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Ming Liao,
Dianchun Shi,
Yao Wang,
Kai Zhang,
Xin Chen,
Yong Gao,
Aihua Tan,
Qiang Xuan,
Xiaobo Yang,
Yanlin Hu,
Xue Qin,
Haiying Zhang, Zengnan Mo
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ABSTRACT: Immunoglobulin E (IgE) provides important information on the humoral immune status, and the IgE level is routinely detected in clinical practice. There are many diseases associated with IgE, such as atopic disease, autoimmune diseases, and so on. IgE is a genetically complex trait, but comprehensive genetic assessment of the variability in serum IgE levels is lacking. Previous genome-wide association studies (GWAS) on total serum IgE levels have identified FCER1A as the susceptibility locus; however, the candidate gene association study in southern Chinese patients reported no association. Given the genetic difference in different populations, we firstly conducted this two-stage GWAS in a Chinese population of 3,495 men, including 1,999 unrelated subjects in the first stage and 1,496 independent individuals replicated in the second stage. In the first stage, we totally identified three single nucleotide polymorphisms (SNPs) which reached a P value of 1.0 × 10(-5). Rs17090302 on chromosome 3 and Rs28708846 on chromosome 13 are intergenic. Rs432085 from chromosome 3p28 is located in the gene CCDC50. When the two-stage data was combined, none of the SNPs reached the genome-wide significant level. Collectively, we did not identify novel loci associated with the serum IgE level in Chinese males, but we hypothesized that CCDC50 was a candidate gene in regulation on IgE level.
Immunogenetics 05/2013; · 2.93 Impact Factor
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Jiange Zhang,
Xianghua Huang,
Ming Liao,
Yong Gao,
Aihua Tan,
Xiaobo Yang,
Haiying Zhang,
Linjian Mo,
Youjie Zhang,
Zheng Lu,
Chunlei Wu,
Yanling Hu, Zengnan Mo
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ABSTRACT: BACKGROUND: Metabolic syndrome (MetS) is often beneficial from testosterone replacement therapy. Although testosterone and sex hormone-binding globulin (SHBG) are inversely associated with the risk of MetS, it is controversial whether the association between testosterone and MetS is independent of SHBG. METHODS: Testosterone, sex hormone binding globulin (SHBG) and MetS were evaluated in 2361 men aged 20-73 years, who participated in the population-based Fangchenggang Area Male Health and Examination Survey (FAMHES). Total testosterone (TT), SHBG and other biochemical profiles were measured. Free testosterone (FT) and bio-available testosterone (BT) were calculated based on Vermeulen's formula. MetS was defined according to NCEP-ATP III criteria for Asian population. The independent associations with MetS were determined by multivariate logistic regression analysis. RESULTS: Men with MetS had a lower level of TT, BT, FT or SHBG than those without MetS (all p < 0.001). Both TT and SHBG were inversely correlated with body mass index (BMI) or homeostasis model assessment of insulin resistance (HOMA-IR) (all age-adjusted p < 0.001). Men within the lowest quartile of TT (OR = 4.86, 95%CI = 2.72-8.68), BT (OR = 3.04, 95%CI = 1.81-5.10), FT (OR = 3.08, 95%CI = 1.81-5.27) or SHBG (OR = 4.28, 95%CI = 2.52-7.27) had a risk of MetS after adjusting for age, smoking, HOMA-IR and BMI. TT remained inversely associated with MetS after further adjusting for SHBG (OR = 0.95, 95%CI = 0.92-0.99), while SHBG remained inversely associated with MetS after further adjusting for TT (OR = 0.99, 95%CI = 0.97-1.00). CONCLUSION: TT and SHBG are independent risk factors of MetS. Prospective studies are needed to explore whether the association between sex hormones and MetS was mediated by insulin resistance or obesity. Copyright © 2013 John Wiley & Sons, Ltd.
Diabetes/Metabolism Research and Reviews 03/2013; · 3.37 Impact Factor
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ABSTRACT: To explore the distribution characteristics of leukocytes in expressed prostatic secretions (EPS) in a large Chinese male population and the correlation with leukocytes and prostate-specific antigen (PSA) levels.
From September to December 2009, EPS specimens were collected from 2504 men (age 20-69 years) who had undergone prostatic massage and were recruited from a large-scale community-based population survey in Southern China. The EPS specimens were divided into 5 categories according to the leukocyte count. The lifestyle and demographic characteristics were obtained by questionnaire. Asymptomatic and symptomatic men were defined according to the findings from the National Institutes of Health-Chronic Prostatitis Symptom Index questionnaire.
EPS specimens were successfully collected from 1779 of the 2504 participants (71%). The degree of inflammation in the EPS specimens progressively increased with age, education, and body mass index (P <.001 for trend for all). A similar result was observed for men living with a partner compared with those living alone (P <.001) but not for men who smoked (P = .084) or consumed alcohol (P = .461). Moreover, a trend for PSA levels increasing progressively across leukocyte categories was observed (P <.001). The PSA levels were greater in all participants with inflammation than in those without (P <.001 for all) when inflammation was defined at 5+, 10+, and 20+ but not for 20+ in asymptomatic men and or not for 5+ and 10+ in symptomatic men.
The results of the present study have shown that the degree of inflammation in EPS progressively increases with increasing age, body mass index, and education. Moreover, an increase of leukocytes in the EPS specimen correlated with increasing PSA levels. Prospective studies are needed to determine whether the minor elevations have clinical significance for prostatitis assessment.
Urology 02/2013; 81(2):384-9. · 2.43 Impact Factor
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ABSTRACT: PURPOSE: Genetic variations are related to individual differences of DNA repair ability and drug metabolism, which can greatly influence prognosis of antineoplastic agents, such as oxaliplatin. The aim was to explore the influences of X-ray repair cross-complementing 1(XRCC1) and Glutathione S-transferase P1 (GSTP1) genetic variants on prognosis of oxaliplatin-based chemotherapy in colorectal cancer patients. METHODS: We performed a meta-analysis including 13 original studies with a total number of 1,234 patients in advanced or metastatic colorectal cancer. Tumor responses [complete response, partial response, stable disease (SD) and progressive disease (PD)] and progression-free survival were estimated. RESULTS: Our results showed that XRCC1 Arg399Gln polymorphism was significantly associated with tumor chemotherapy when SD or PD was considered as non-response [risk ratio (RR) = 1.29; 95 % confidence intervals (CI): 1.05-1.60; P = 0.02]. No significant association was found between GSTP1 Ile105 Val polymorphism and tumor response (RR = 0.63; 95 % CI: 0.35-1.14; P = 0.13). In addition, our results also showed that there was no significant association between XRCC1 codon 399 Arg/Gln or Gln/Gln genotypes and hazard ratio for progression-free survival (Hazards ratio = 1.04 and 1.92; 95 % CI: 0.75-1.43 and 0.62-1.37; P = 0.826 and 0.677, respectively). CONCLUSION: In our meta-analysis, XRCC1 Arg399Gln polymorphism may be a valuable genetic marker for oxaliplatin-based chemotherapy in colorectal cancer, and the results still need further confirmation.
Cancer Chemotherapy and Pharmacology 01/2013; · 2.83 Impact Factor
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Meian He,
Chen Wu,
Jianfeng Xu,
Huan Guo,
Handong Yang,
Xiaomin Zhang,
Jielin Sun,
Dianke Yu,
Li Zhou,
Tao Peng, [......],
Weimin Fang,
Yuan Liang,
Yun Zhai,
Weihong Chen,
Xiaoping Miao,
Gangqiao Zhou,
Frank B Hu,
Dongxin Lin, Zengnan Mo,
Tangchun Wu
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ABSTRACT: OBJECTIVE: Tumour biomarkers are used as indicators for cancer screening and as predictors for therapeutic responses and prognoses in cancer patients. We aimed to identify genetic loci that influence concentrations of cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and α fetoprotein (AFP), and investigated the associations between the significant single nucleotide polymorphisms (SNPs) with risks of oesophageal squamous cell (OSCC), pancreatic and hepatocellular cancers. DESIGN: We carried out a genome wide association study on plasma CA19-9, CEA and AFP concentrations in 3451 healthy Han Chinese and validated the results in 10 326 individuals. Significant SNPs were further investigated in three case control studies (2031 OSCC cases and 2044 controls; 981 pancreatic cancer cases and 1991 controls; and 348 hepatocellular cancer cases and 359 controls). RESULTS: The analyses showed association peaks on three genetic loci for CA19-9 (FUT6-FUT3 at 19p13.3, FUT2-CA11 at 19q13.3 and B3GNT3 at 19p13.1; p=1.16×10(-13)-3.30×10(-290)); four for CEA (ABO at 9q34.2, FUT6 at 19p13.3, FUT2 at 19q13.3 and FAM3B at 21q22.3; p=3.33×10(-22)-5.81×10(-209)); and two for AFP (AFP at 4q11-q13 and HISPPD2A at 15q15.3; p=3.27×10(-18) and 1.28×10(-14)). These explained 17.14% of the variations in CA19-9, 8.95% in CEA and 0.57% in AFP concentrations. Significant ABO variants were also associated with risk of OSCC and pancreatic cancers, and AFP variants with risk of hepatocellular cancer (p<0.05). CONCLUSIONS: This study identified several loci associated with CA19-9, CEA and AFP concentrations. The ABO variants were associated with risk of OSCC and pancreatic cancers and AFP variants with risk of hepatocellular cancer.
Gut 01/2013; · 10.11 Impact Factor
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Jielin Sun,
Sha Tao,
Yong Gao,
Tao Peng,
Aihua Tan,
Haiying Zhang,
Xiaobo Yang,
Xue Qin,
Yanling Hu,
Junjie Feng, [......],
Zhengjia Liang,
Deyi Shi,
Zhang Huang,
Xianghua Huang,
Ming Liu,
Qian Liu,
Shijun Zhang,
S Lilly Zheng,
Jianfeng Xu, Zengnan Mo
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ABSTRACT: Prostate-specific antigen (PSA) is a commonly used cancer biomarker for prostate cancer, and is often included as part of routine physical examinations in China. Serum levels of PSA may be influenced by genetic factors as well as other factors. A genome-wide association study (GWAS) conducted in a European population successfully identified six genetic loci that were significantly associated with PSA level. In this study, we aimed to identify common genetic variants that are associated with serum level of PSA in a Chinese population. We also evaluated the effects of those variants by creating personalized PSA cutoff values. A two-stage GWAS of PSA level was performed among men age 20-69 years and self-reported cancer-free participants that underwent routine physical examinations at several hospitals in Guangxi Province, China. Single nucleotide polymorphisms (SNPs) significantly associated with PSA levels in the first stage of sample (N = 1,999) were confirmed in the second stage of sample (N = 1,496). Multivariate linear regression was used to assess the independent contribution of confirmed SNPs and known covariates, such as age, to the level of PSA. SNPs in three regions were significantly associated with levels of PSA in this two-stage GWAS, and had combined P values between 4.62 × 10(-17) and 6.45 × 10(-37). The three regions are located on 1q32.1 at SLC45A3, 10q11.23 at MSMB, and 19q13.33 at KLK3. The region 1q32.1 at SLC45A3 was identified as a novel locus. Genetic variants contributed significantly more to the variance of PSA level than known covariates such as age. Personalized cutoff values of serum PSA, calculated based on the inheritance of these associated SNPs, differ considerably among individuals. Identification of these genetic markers provides new insight into the molecular mechanisms of PSA. Taking individual variation into account, these genetic variants may improve the performance of PSA to predict prostate cancer.
Human Genetics 12/2012; · 5.07 Impact Factor
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De-Ke Jiang,
Jielin Sun,
Guangwen Cao,
Yao Liu,
Dongxin Lin,
Yu-Zhen Gao,
Wei-Hua Ren,
Xi-Dai Long,
Hongxing Zhang,
Xiao-Pin Ma, [......],
Wei Zheng,
Xiao-Ou Shu, Zengnan Mo,
Yin Yao Shugart,
Xue-Jun Zhang,
Gangqiao Zhou,
Hongbing Shen,
S Lilly Zheng,
Jianfeng Xu,
Long Yu
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ABSTRACT: To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P(meta) = 2.48 × 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P(meta) = 2.72 × 10(-17), OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P(trend) = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 × 10(-14)).
Nature Genetics 12/2012; · 35.53 Impact Factor
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ABSTRACT: Recent reports indicate prostaglandin E2 (PGE2) can modulate tumor environment and promote angiogenesis through induction of stromal cell-derived factor 1 (SDF-1) production. We investigated the mechanism of PGE2-induced SDF-1 regulation in human prostate stromal cell and analyzed the effects in a stromal-epithelial interaction model. PGE2 stimulation increased SDF-1 expression in the prostate stromal cell lines WPMY-1 and NAF. We revealed signaling through the PGE2 receptor EP3 and activation of protein kinase A (PKA) are required. The EP3 agonist sulprostone and the cAMP analogue forskolin mimicked and the EP3 siRNA, antagonist L798106 and the PKA inhibitor H89 abrogated the effect of PGE2 on SDF-1 expression. SDF-1 promoter truncation experiments demonstrated a 254bp (from nt -219 to nt +34) SDF-1 proximal promoter fragment containing 5 putative transcription factor Sp1 binding motifs is sufficient for PGE2 induction. CHIP assays confirmed binding and PGE2 induced recruitment of Sp1 to the SDF-1 promoter. Sp1 motif mutation identified Sp1 motifs -140/-133 and -9/+1 as the crucial elements responsible for PGE2 induction. Moreover, SDF-1 was up- or down-regulated by Sp1 over-expression or knock-down. We also demonstrate stimulation of migration of prostate cancer cell lines PC3 and DU145 with conditioned media collected from WPMY-1 or NAF cells stimulated with PGE2 and blockade of enhanced migration by a SDF-1 neutralizing antibody. In conclusion, we provide evidence for a paracrine prostate stromal-epithelial interaction induced by upregulation of expression of SDF-1 by PGE2. Our research provides new insights into the mechanism promoting metastasis of prostate carcinoma via stromal-epithelial interaction.
The international journal of biochemistry & cell biology 12/2012; · 4.89 Impact Factor
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ABSTRACT: OBJECTIVE: To determine the potential effect of metabolic syndrome (MetS) and its components on erectile dysfunction (ED) in Chinese men. MATERIALS AND METHODS: Data were collected from the Fangchenggang Area Male Healthy and Examination Survey from September 2009 to December 2009, and 3197 men were finally included. The MetS was defined using the updated National Cholesterol Education Program Adult Treatment Panel III for Asian Americans. ED was assessed using the 5-item International Index Erectile Function. The association between MetS and ED is presented as the odds ratios (ORs), with 95% confidence intervals (CIs) estimated using a logistic regression model. RESULTS: After adjustments for age, smoking, alcohol drinking, physical activity, education, and body mass index, our results showed that subjects with MetS had a significantly greater risk of ED (OR 1.34, 95% CI 1.04-1.72; P = .02), especially in middle-age (40-59 years) men (OR 2.43, 95% CI 1.71-3.47; P <.001). Of the MetS components, abnormal fasting blood glucose was the most significantly independent factor of MetS for ED (OR 1.31, 95% CI 1.11-1.55; P = .002). CONCLUSION: Our data have shown that MetS is a potential and independent risk factor for ED in Chinese men, especially in middle-age men, MetS can be recognized as a warning signal for ED. Abnormal fasting blood glucose was the most significantly independent factor of MetS for ED in Chinese men.
Urology 10/2012; · 2.43 Impact Factor
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Jianfeng Xu, Zengnan Mo,
Dingwei Ye,
Meilin Wang,
Fang Liu,
Guangfu Jin,
Chuanliang Xu,
Xiang Wang,
Qiang Shao,
Zhiwen Chen, [......],
Xiao-Ou Shu,
Wei Zheng,
Hongbing Shen,
Li Jin,
Rong Shi,
Daru Lu,
Xuejun Zhang,
Jielin Sun,
S Lilly Zheng,
Yinghao Sun
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ABSTRACT: Prostate cancer risk-associated variants have been reported in populations of European descent, African-Americans and Japanese using genome-wide association studies (GWAS). To systematically investigate prostate cancer risk-associated variants in Chinese men, we performed the first GWAS in Han Chinese. In addition to confirming several associations reported in other ancestry groups, this study identified two new risk-associated loci for prostate cancer on chromosomes 9q31.2 (rs817826, P = 5.45 × 10(-14)) and 19q13.4 (rs103294, P = 5.34 × 10(-16)) in 4,484 prostate cancer cases and 8,934 controls. The rs103294 marker at 19q13.4 is in strong linkage equilibrium with a 6.7-kb germline deletion that removes the first six of seven exons in LILRA3, a gene regulating inflammatory response, and was significantly associated with the mRNA expression of LILRA3 in T cells (P < 1 × 10(-4)). These findings may advance the understanding of genetic susceptibility to prostate cancer.
Nature Genetics 09/2012; · 35.53 Impact Factor
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ABSTRACT: OBJECTIVES: Abnormal alanine aminotransferase (ALT) activity is indicative of liver disease even a burden of overall health. We assessed the factors associated with ALT activity and their internal relationships in a male population from southern China. DESIGN AND METHODS: Data of physical examinations, laboratory tests, hepatic ultrasounds and standardized questionnaire were collected from 2119 males participating in a population-based survey from September 2009 to December 2009. RESULTS: Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) were associated with the elevation of ALT levels (P<0.05). Prevalence of NAFLD was correlated to MetS (r=0.991, P=0.009). The levels of abnormal metabolic syndrome components increased in proportion with the ALT elevation (P<0.01). Obesity and hyperlipidemia were associated with the ALT levels in multivariate regression analysis (P<0.01). There was no synergic effect of hepatitis B virus surface antigen (HBsAg) and MetS on the ALT levels (synergy index [SI]=0.74, 95% confidence interval [CI]: 0.71-0.80). CONCLUSION: NAFLD and MetS were associated with ALT levels in a male population from southern China. Obesity and hyperlipidemia were independent MetS components contributing to elevated ALT (e-ALT). This finding might suggest necessity on justification of these confounding factors when detecting ALT levels among this population.
Clinical biochemistry 09/2012; · 2.02 Impact Factor
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Xiaobo Yang,
Jielin Sun,
Yong Gao,
Aihua Tan,
Haiying Zhang,
Yanling Hu,
Junjie Feng,
Xue Qin,
Sha Tao,
Zhuo Chen, [......],
Deyi Shi,
Zhang Huang,
Xianghua Huang,
Ming Liu,
Qian Liu,
Shijun Zhang,
Jeffrey M Trent,
S Lilly Zheng,
Jianfeng Xu, Zengnan Mo
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ABSTRACT: Complement C3 and C4 play key roles in the main physiological activities of complement system, and their deficiencies or over-expression are associated with many clinical infectious or immunity diseases. A two-stage genome-wide association study (GWAS) was performed for serum levels of C3 and C4. The first stage was conducted in 1,999 healthy Chinese men, and the second stage was performed in an additional 1,496 subjects. We identified two SNPs, rs3753394 in CFH gene and rs3745567 in C3 gene, that are significantly associated with serum C3 levels at a genome-wide significance level (P = 7.33×10(-11) and P = 1.83×10(-9), respectively). For C4, one large genomic region on chromosome 6p21.3 is significantly associated with serum C4 levels. Two SNPs (rs1052693 and rs11575839) were located in the MHC class I area that include HLA-A, HLA-C, and HLA-B genes. Two SNPs (rs2075799 and rs2857009) were located 5' and 3' of C4 gene. The other four SNPs, rs2071278, rs3763317, rs9276606, and rs241428, were located in the MHC class II region that includes HLA-DRA, HLA-DRB, and HLA-DQB genes. The combined P-values for those eight SNPs ranged from 3.19×10(-22) to 5.62×10(-97). HBsAg-positive subjects have significantly lower C3 and C4 protein concentrations compared with HBsAg-negative subjects (P<0.05). Our study is the first GWAS report which shows genetic components influence the levels of complement C3 and C4. Our significant findings provide novel insights of their related autoimmune, infectious diseases, and molecular mechanisms.
PLoS Genetics 09/2012; 8(9):e1002916. · 8.69 Impact Factor
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Xiaoling Lin,
Lianxi Qu,
Zhuo Chen,
Chuanliang Xu,
Dingwei Ye,
Qiang Shao,
Xiang Wang,
Jun Qi,
Zhiwen Chen,
Fangjian Zhou, [......],
Rong Na,
Qiang Ding,
Daru Lu,
Rong Shi,
Jielin Sun,
Fang Liu,
S Lilly Zheng, Zengnan Mo,
Yinghao Sun,
Jianfeng Xu
[show abstract]
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ABSTRACT: BACKGROUND: A rare mutation G84E in HOXB13 was recently identified to be associated with prostate cancer (PCa) in Caucasians. The goal of this study is to test association between HOXB13 genetic variants and PCa risk in Chinese men. METHODS: All study subjects were part of the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa). In the first stage, we screened for mutations by sequencing the HOXB13 coding region in 96 unrelated PCa patients. In stage 2, G84E and novel mutations found in stage 1 were genotyped in 671 PCa patients and 1,536 controls. In stage 3, mutation status in 751 additional PCa patients was imputed via haplotype. RESULTS: The G84E mutation was not detected in this study. However, a novel mutation, G135E, was identified among 96 patients in stage 1. It was also observed twice in 575 additional PCa patients but not in 1,536 control subjects of stage 2. The frequency of G135E was significantly different between cases and controls, with a P-value of 0.027, based on Fisher's exact test. Haplotype estimation showed that G135E mutation carriers shared a unique haplotype that was not observed in other subjects. In stage 3, two more PCa patients were predicted to carry the G135E mutation. CONCLUSIONS: We identified a novel rare mutation in the HOXB13 gene, G135E, which appears to be a founder mutation. This mutation is associated with increased PCa risk in Chinese men. Consistent with a previous report, our findings provide further evidence that rare mutations in HOXB13 contribute to PCa risk. Prostate © 2012 Wiley Periodicals, Inc.
The Prostate 06/2012; · 3.48 Impact Factor
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Xiaoling Lin,
Daru Lu,
Yong Gao,
Sha Tao,
Xiaobo Yang,
Junjie Feng,
Aihua Tan,
Haiying Zhang,
Yanling Hu,
Xue Qin,
Seong-Tae Kim,
Tao Peng,
Li Li,
Linjian Mo,
Shijun Zhang,
Jeffrey M Trent, Zengnan Mo,
S Lilly Zheng,
Jianfeng Xu,
Jielin Sun
[show abstract]
[hide abstract]
ABSTRACT: Vitamin B12 (VitB12 or cobalamin) is an essential cofactor in several metabolic pathways. Clinically, VitB12 deficiency is associated with pernicious anemia, neurodegenerative disorder, cardiovascular disease and gastrointestinal disease. Although previous genome-wide association studies (GWAS) identified several genes, including FUT2, CUBN, TCN1 and MUT, that may influence VitB12 levels in European populations, common genetic determinants of VitB12 remain largely unknown, especially in Asian populations. Here we performed a GWAS in 1999 healthy Chinese men and replicated the top findings in an independent Chinese sample with 1496 subjects. We identified four novel genomic loci that were significantly associated with serum level of VitB12 at a genome-wide significance level of 5.00 × 10(-8). These four loci were MS4A3 (11q12.1; rs2298585; P= 2.64 × 10(-15)), CLYBL (13q32; rs41281112; P= 9.23 × 10(-10)), FUT6 (19p13.3; rs3760776; P= 3.68 × 10(-13)) and 5q32 region (rs10515552; P= 3.94 × 10(-8)). In addition, we also confirmed the association with the serum level of VitB12 for the previously reported FUT2 gene and identified one novel non-synonymous single-nucleotide polymorphism in FUT2 gene in this Chinese population (19q13.33; rs1047781; P= 3.62 × 10(-36)). The new loci identified offer new insights into the biochemical pathways involved in determining the serum level of VitB12 and provide opportunities to better delineate the role of VitB12 in health and disease.
Human Molecular Genetics 03/2012; 21(11):2610-7. · 7.64 Impact Factor
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Youjie Zhang,
Yong Gao,
Aihua Tan,
Xiaobo Yang,
Haiying Zhang,
Shijun Zhang,
Chunlei Wu,
Zheng Lu,
Mengjie Wang,
Ming Liao,
Xue Qin,
Li Li,
Yanling Hu, Zengnan Mo
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ABSTRACT: OBJECTIVE: To examine the association of endogenous sex hormones and SHBG with C-reactive protein (CRP) in Chinese men. DESIGN AND PARTICIPANTS: The study population comprised 1989 men at baseline recruitment of a population-based cohort in China. Participant information on risk factors was collected by a face-to-face interview and clinical examination. All subjects in the study were without taking any kind of medication for anti-inflammation purpose or treatment of hypogonadism and with CRP value less than 10 mg/L. Data were analyzed by using linear regression analyses. RESULTS: Higher levels of total testosterone (TT, β = -0.114, 95%CI, -0.162 to -0.065), free testosterone (β = -0.059, 95%CI, -0.106 to -0.012) and SHBG (β = -0.116, 95%CI, -0.169 to -0.063) were statistically significantly related to lower levels of CRP, after adjustment for age, waist circumference (WC), triglycerides, high-density lipoprotein cholesterol, fasting glucose, insulin, smoking status, hypertension, diabetes and family history of hypertension or diabetes. In the subgroup of men with body mass index ≥27.5 kg/m(2) or with metabolic syndrome, findings for TT and SHBG were more pronounced, whereas the associations of TT with CRP were attenuated and nonstatistically significant among subjects with WC ≥90 cm or with insulin resistance. No associations were observed between estradiol, LH, FSH and CRP. CONCLUSIONS: We have confirmed the association of androgens with reduced inflammation as measured by CRP in Chinese men. This is independent of conventional cardiovascular risk factors and was explained in part by markers of central obesity and insulin resistance, rather than metabolic syndrome. © 2012 Blackwell Publishing Ltd.
Clinical Endocrinology 02/2012; · 3.17 Impact Factor
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Xue Qin,
Hui Lv, Zengnan Mo,
Zhiping Chen,
Liwen Lin,
Tao Peng,
Haiying Zhang,
Xiaobo Yang,
Yong Gao,
Aihua Tan,
Shan Huang,
Haiwei Li,
Huiling Wu,
Yan Deng,
Shan Li
[show abstract]
[hide abstract]
ABSTRACT: The aim was to establish reference intervals for serum sex hormones in adult men in the Fangchenggang area of China.
Serum samples from 1,191 healthy male subjects, aged 20 - 69 years, were collected from the Fangchenggang Area Male Health and Examination Survey (FAMHES). Total testosterone (T), estrogen (E2), luteinising hormone (LH), follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) were measured by electrochemiluminescence immunoassay (Elecsys). Free testosterone (FTc) was calculated from the concentrations of T, SHBG, and albumin.
The total nonparametric reference intervals for male sex hormones in our study were 12.6 - 37.0 nmol/L for T, 0.24 - 0.69 nmol/L for FTc, 65.4 - 207.7 pmol/L for E2, 2.2 - 11.6 IU/L for LH, 1.8 - 16.5 IU/L for FSH, and 18.2 - 95.1 nmol/L for SHBG. Age had a significant positive association with LH (r = 0.218), FSH (r = 0.427), and SHBG (r = 0.427) and a negative association with FTc (r = -0.383) and E2 (r = -0.098), but no significant association with T after adjustment for BMI. The age-dependent reference intervals were also calculated. Higher T and FTc concentrations were found in men who smoke compared with non-smokers, while no significant differences were found in E2, LH, FSH, and SHBG. When stratified for the number of cigarettes smoked per day, we found that the distributions of serum T levels were significantly higher only in the smokers who smoked 11 or more cigarettes a day than the non-smokers. Unlike T, the distributions of serum FTc levels were significantly higher only in the smokers who smoked less than 11 cigarettes a day, while the FSH levels were significantly lower.
In clinical practice, single reference intervals can be used for men aged 20 - 69 years for T and E2 measured with the Elecsys method, but separate age-dependent reference intervals should be used for FTc, LH, FSH, and SHBG. In addition, distinct reference intervals for T should be established for non-smokers or smokers (1 - 10 cigarettes/day) and smokers (> or = 11 cigarettes/day).
Clinical laboratory 01/2012; 58(3-4):281-90. · 0.90 Impact Factor
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Ming Yang,
Yongming Wu,
Yanmei Lu,
Changyuan Liu,
Jielin Sun,
Ming Liao,
Min Qin,
Linjian Mo,
Yong Gao,
Zheng Lu, [......],
Xue Qin,
Yanling Hu,
Shijun Zhang,
Jianling Li,
Min Dong,
S Lilly Zheng,
Jianfeng Xu,
Xiaobo Yang,
Aihua Tan, Zengnan Mo
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ABSTRACT: IgM provides a first line of defense during microbial infections. Serum IgM levels are detected routinely in clinical practice. And IgM is a genetically complex trait. We conducted a two-stage genome-wide association study (GWAS) to identify genetic variants affecting serum IgM levels in a Chinese population of 3495, including 1999 unrelated subjects in the first stage and 1496 independent individuals in the second stage. Our data show that a common single nucleotide polymorphism (SNP), rs11552708 located in the TNFSF13 gene was significantly associated with IgM levels (p = 5.00×10(-7) in first stage, p = 1.34×10(-3) in second stage, and p = 4.22×10(-9) when combined). Besides, smoking was identified to be associated with IgM levels in both stages (P<0.05), but there was no significant interaction between smoking and the identified SNP (P>0.05). It is suggested that TNFSF13 may be a susceptibility gene affecting serum IgM levels in Chinese male population.
PLoS ONE 01/2012; 7(10):e47990. · 4.09 Impact Factor
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Ming Liao,
Xianghua Huang,
Yong Gao,
Aihua Tan,
Zheng Lu,
Chunlei Wu,
Youjie Zhang,
Xiaobo Yang,
Haiying Zhang,
Xue Qin, Zengnan Mo
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ABSTRACT: Testosterone is essential for the regulation of erectile physiology, but the relationship between low testosterone and erectile dysfunction (ED) has not been firmly established.
To examine the association between serum total, free and bio-available testosterone and ED in a population-based sample.
A consecutive series of 1776 men aged 20-77 participated in the routine physical examination from September 2009 to December 2009 in Guangxi, China. ED was assessed using the five-item International Index of Erectile Function (IIEF-5) questionnaire. Total testosterone (TT), sex hormone binding globulin (SHBG) and other biochemical profiles were measured. Free testosterone (FT) and bio-available testosterone (BT) were calculated based on Vermeulen's formula. Data were collected with regard to smoking, alcoholic drinking, physical activity and metabolic syndrome.
The prevalence of ED (IIEF-5<22) was 47.6%. Men with ED were significantly older, and more prone to smoke cigarettes (≥20 cigarettes/day) or drink alcohol (≥3 drinks/week), and more likely to have elevated blood pressure (P = 0.036) or hyperglycemia (P<0.001) compared with those without ED. The significant increase in SHBG with age was parallel to its increase with increasing severity of ED (P<0.001). The obscure increase in TT across the ED status was detected without significance (P = 0.418), but TT was positively associated with ED after adjustment for age [odds ratio (OR) = 1.02, 95% CI (confidence internal): 1.00-1.04]. FT and BT were inversely associated with ED (OR = 0.14, 95%CI: 0.06-0.33; OR = 0.92 (95%CI: 0.89-0.96, respectively) in the univariate analysis, and this inverse association appeared to be independent of smoking status, alcoholic drinking, physical activity, hyper-triglyceridemia and hyperglycemia.
FT and BT are inversely related to worsening ED, whereas the positive association between TT and ED is most likely due to the increase in SHBG.
PLoS ONE 01/2012; 7(6):e39234. · 4.09 Impact Factor
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Wanqing Wen,
Yoon-Shin Cho,
Wei Zheng,
Rajkumar Dorajoo,
Norihiro Kato,
Lu Qi,
Chien-Hsiun Chen,
Ryan J Delahanty,
Yukinori Okada,
Yasuharu Tabara, [......],
Wei Lu,
Mitsuhiro Yokota,
Mark Seielstad,
Cathy S J Fann,
Jer-Yuarn Wu,
Jong-Young Lee,
Frank B Hu,
Toshihiro Tanaka,
E Shyong Tai,
Xiao-Ou Shu
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ABSTRACT: Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We performed a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 east Asians, which was followed by in silico and de novo replication studies in 37,691 and 17,642 additional east Asians, respectively. We identified ten BMI-associated loci at genome-wide significance (P < 5.0 × 10(-8)), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR-QPCTL, ADCY3-DNAJC27, BDNF and MAP2K5) and three novel loci in or near the CDKAL1, PCSK1 and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a newly identified signal near PAX6, all of which were associated with BMI with P < 5.0 × 10(-7). Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations.
Nature Genetics 01/2012; 44(3):307-11. · 35.53 Impact Factor
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Aihua Tan,
Jielin Sun,
Ning Xia,
Xue Qin,
Yanling Hu,
Shijun Zhang,
Sha Tao,
Yong Gao,
Xiaobo Yang,
Haiying Zhang, [......],
Zhengjia Liang,
Deyi Shi,
Zhang Huang,
Xianghua Huang,
Ming Liu,
Qiang Ding,
Jeffrey M Trent,
S Lilly Zheng, Zengnan Mo,
Jianfeng Xu
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ABSTRACT: Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Gene-environment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 × 10(-26) and 1.41 × 10(-9) for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P = 3.34 × 10(-5)). Rs671 was significantly associated with serum TG levels in drinkers (P = 1.90 × 10(-10)), while no association was observed in non-drinkers (P > 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P = 1.28 × 10(-8) for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.
Human Molecular Genetics 12/2011; 21(7):1658-64. · 7.64 Impact Factor
