[Show abstract][Hide abstract] ABSTRACT: Sex hormones and gonadotropins exert a wide variety of effects in physiological and pathological processes. Accumulated evidence shows a strong heritable component of circulating concentrations of these hormones. Recently, several genome-wide association studies (GWASs) conducted in Caucasians have identified multiple loci that influence serum levels of sex hormones. However, the genetic determinants remain unknown in Chinese populations. In this study, we aimed to identify genetic variants associated with major sex hormones, gonadotropins, including testosterone, oestradiol, follicle-stimulating hormone (FSH), luteinising hormone (LH) and sex hormone binding globulin (SHBG) in a Chinese population.
A two-stage GWAS was conducted in a total of 3495 healthy Chinese men (1999 subjects in the GWAS discovery stage and 1496 in the confirmation stage).
We identified a novel genetic region at 15q21.2 (rs2414095 in CYP19A1), which was significantly associated with oestradiol and FSH in the Chinese population at a genome-wide significant level (p=6.54×10(-31) and 1.59×10(-16), respectively). Another single nucleotide polymorphism in CYP19A1 gene was significantly associated with oestradiol level (rs2445762, p=7.75×10(-28)). In addition, we confirmed the previous GWAS-identified locus at 17p13.1 for testosterone (rs2075230, p=1.13×10(-8)) and SHBG level (rs2075230, p=4.75×10(-19)) in the Chinese population.
This study is the first GWAS investigation of genetic determinants of FSH and LH. The identification of novel susceptibility loci may provide more biological implications for the synthesis and metabolism of these hormones. More importantly, the confirmation of the genetic loci for testosterone and SHBG suggests common genetic components shared among different ethnicities.
Journal of Medical Genetics 09/2013; · 5.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: The goal of present study was to examine the influence of demographic characteristics, lifestyle, and metabolic factors on pressure-induced pain threshold. DESIGN AND SETTING: The study population comprised 2,517 healthy men at second-phase recruitment of a population-based cohort in China. The pressure pain threshold (PPT) at two locations, triceps and inguinal lines, was obtained using a digital pressure algometer. Education and occupation, as well as lifestyle factors, were self-reported in a face-to-face interview. Blood lipid and fasting glucose were measured as a routine healthy check-up program. RESULTS: A lower PPT was found among men with younger age, higher level of education, and non-manual occupation. In addition, men with central obesity and moderate leisure time physical exercise were more sensitive to muscle mechanical stimuli. PPT was significantly correlated with high-density lipoprotein cholesterol (β for triceps = 0.064, and β for inguinal lines = 0.052) in a multivariate linear regression model, after controlling for multiple variables. Elevated PPT was also found among subjects with hyperglycemia (both P for triceps and inguinal lines <0.001) and excess drinking (P for triceps = 0.005). CONCLUSIONS: It is important for physicians and researchers to consider these variables when evaluating pain sensitivity in clinic and in research. The underling mechanisms between these factors and pressure pain perception are worthy of further exploration.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Increased serum uric acid (SUA) levels may be involved in the development of non-alcoholic fatty liver disease (NAFLD) in men presenting with metabolic syndrome (MetS) and/or insulin resistance. We aimed to determine the independent relationship between SUA and NAFLD in non-diabetic Chinese male population, and to explore the determinants of SUA levels among indexes of adiposity, lipid, and genotypes pertaining to triglycerides metabolism, inflammation, oxidative stress, and SUA concentrations. A total of 1440 men, classified depending on the presence of ultrasonographically detected NAFLD, underwent a complete healthy checkup program. Genotypes were extracted from our previously established genome-wide association study database. After adjusting for age, smoking, drinking, body mass index, homeostasis model assessment of insulin resistance, C-reactive protein, creatinine, alanine aminotransferase (ALT) and components of metabolic syndrome, the odds ratio for NAFLD, comparing the highest with the lowest SUA quartile, was 2.81 (95% confidence interval 1.66-4.76). A stepwise multivariate linear regression analysis (R(2) = 0.238, P<0.001) retained age, waist circumference, serum creatinine, triglycerides, the Q141K variant in ABCG2 (rs2231142) and NAFLD as significant predictors of SUA levels (all P<0.001). Besides, ALT and Met196Arg variant in TNFRSF1B (rs1061622) additionally associated with SUA among individuls with NAFLD. Our data suggest that in Chinese men, elevated SUA is significantly associated with NAFLD, independent of insulin resistance and other metabolic disorders, such as central obesity or hypertriglyceridemia. Meanwhile, among subjects with NAFLD, index of liver damage, such as elevated ALT combined with genetic susceptibility to inflammation associated with increased SUA levels.
PLoS ONE 01/2013; 8(7):e67152. · 3.53 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Highlights
► pCO2 levels range from 230 to 8300 μatm with an average of 1230 μatm. ► High-temporal-resolution sampling shows obvious daily and seasonal variations. ► CO2 degassing flux is 27 mol/m2/yr, with the upper limit of 50 mol/m2/yr. ► Net CO2 flux and pCO2 were strongly correlated with dissolved nitrogen and pH. ► River’s roles on carbon cycling are determined, 7% of carbon from catchment emits.
Journal of Hydrology 10/2012; 466–467:141-150. · 2.96 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Methyl helicterate is a triterpenoid isolated from Helicteres angustifolia (Sterculiaceae), one of the valuable traditional Chinese herbs. Antifibrotic activities of H. angustifolia have been extensively proved.
The purpose of this study was to investigate the effect of methyl helicterate (MH) on liver fibrosis in rats induced by carbon tetrachloride (CCl(4)) and to explore its underlying mechanism.
Hepatic fibrosis was induced in male Sprague-Dawley (SD) rats by intragastric administration with 2ml/kg CCl(4) (mixed 1:1 in peanut oil) twice a week for 12 weeks. To evaluate the effect of MH (16.72, 33.45, 66.90mg/kg) on hepatic fibrosis, liver function, histological study and hepatic fibrosis evaluation were performed. Liver function was assessed by determining the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb) and total protein (TP). The biomarkers such as hydroxyproline (Hyp), hyaluronic acid (HA), type III precollagen (PCIII) and laminin (LN) were examined for the evaluation of hepatic fibrosis. The underlying mechanism was investigated by measuring oxidative stress level and detecting the expression of TGF-β1 mRNA and Smad3 protein.
MH (33.45, 66.90mg/kg) treatment significantly inhibited the loss of body weight and the increase of liver index in rats induced by CCl(4). MH also improved the liver function as indicated by decreasing serum enzymatic activities of ALT, AST, TP and Alb (P<0.05). Histological results indicated that MH alleviated liver damage and reduced the formation of fibrous septa. Moreover, MH significantly decreased liver Hyp, HA, LN and PCIII (P<0.05). Research on mechanism showed that MH could markedly reduce liver malondialdehyde (MDA) concentration, increase activities of liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and inhibit the expression of TGF-β1 mRNA and Smad3 protein (P<0.05).
Our findings indicated that MH can inhibit CCl(4)-induced hepatic fibrosis, which may be ascribed to its radical scavenging action, antioxidant activity, and modulation of TGF-β-Smad3 signaling pathway.
Journal of ethnopharmacology 08/2012; 143(3):889-95. · 2.32 Impact Factor
[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. · 7.69 Impact Factor
[Show abstract][Hide abstract] 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. · 7.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fluxes of particulate N (PN), dissolved P (DP), PAP and TP exhibited great seasonality. Dissolved N (DN) and particle associated P (PAP) were the major forms of TN and TP, respectively. Areal export rates of NH4+-N, PN, PAP and TP were higher than in the main channel and most tributaries of the Changjiang River. Better estimates of N and P loads could have been improved with daily sampling, particularly for particulate variables and in high-flow period.
Journal of Hydrology 01/2011; 405(3):344-351. · 2.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Water samples were collected twice per month over a two-year period from the Longchuanjiang River (Yunnan Province, China) to understand monthly variations in major elements and solute fluxes as related to rock weathering and associated CO2 consumption rates. Solute concentrations were 5 times the median of 65mg/l for global average. Total cationic exchange capacity (Tz+) ranged from 2.4 to 6.1meq/l; and the mean (4.4meq/l) was significantly higher than that of the global river waters. Calcium and bicarbonate dominated the annual ionic composition, accounting for more than 70% of the solute flux that exceeded 71×106kg/yr. Lower concentrations of most measured elements during the monsoon high flow period could be explained by dilution effects from precipitation. Three major reservoirs contributed to the dissolved load: carbonates, silicates and anthropogenic inputs, i.e., some 83% of the riverine cations from carbonates and 17% from silicates. The chemical weathering rate of 26.1t/km2/yr, with respective carbonate and silicate weathering rates of 20.3t/km2/yr (8.46mm/kyr) and 5.75t/km2/yr (2.13mm/kyr), was comparable to the average for global rivers, but higher than that for the Changjiang River in China. The CO2 consumption rate was estimated to be 173.7×103mol/km2/yr and 202.9×103mol/km2/yr by silicate and carbonate weathering, respectively. The CO2 consumed by rock chemical weathering in the upper Changjiang River reduced the atmospheric CO2 level and constituted a significant part of the global carbon budget. Consequently the carbon sink potential of rock chemical weathering in the Qinghai-Plateau deserves extra attention. Population density and anthropogenic activities, particularly agricultural practices, contributed remarkably to dissolved solutes and associated CO2 consumption worldwide, and anthropogenic inputs probably contributed some 10.4% to the dissolved solutes in the Longchuanjiang River.