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ABSTRACT: Prenatal development and early childhood are critical periods for establishing the tissue-specific epigenome, and may have a profound impact on health and disease in later life. However, epigenomic profiles at birth and in early childhood remain largely unexplored. The focus of this report is to examine the individual variation and longitudinal pattern of genome-wide DNA methylation levels from birth through the first two years of life in 105 Black children (59 males and 46 females) enrolled at the Boston Medical Center. We performed epigenomic mapping of cord blood at birth and venous blood samples from the same set of children within the first two years of life using Illumina Infinium Humanmethylation27 BeadChip. We observed a wide range of inter-individual variations in genome-wide methylation at each time point including lower levels at CpG islands, TSS200, 5'UTR and 1st Exon locations, but significantly higher levels in CpG shores, shelves, TSS1500, gene body and 3'UTR. We identified CpG sites with significant intra-individual longitudinal changes in the first two years of life throughout the genome. Specifically, we identified 159 CpG sites in males and 149 CpG sites in females with significant longitudinal changes defined by both statistical significance and magnitude of changes. These significant CpG sites appeared to be located within genes with important biological functions including immunity and inflammation. Further studies are needed to replicate our findings, including analysis by specific cell types, and link those individual variations and longitudinal changes with specific health outcomes in early childhood and later life.
Epigenetics: official journal of the DNA Methylation Society 06/2012; 7(6):594-605. · 4.58 Impact Factor
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Hui-Ju Tsai,
Xiumei Hong,
Jinbo Chen,
Xin Liu,
Colleen Pearson,
Katherin Ortiz,
Emmet Hirsch,
Linda Heffner,
Daniel E Weeks,
Barry Zuckerman,
Xiaobin Wang
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ABSTRACT: To estimate whether African ancestry, specific gene polymorphisms, and gene-environment interactions could account for some of the unexplained preterm birth variance within African American women.
We genotyped 1,509 African ancestry-informative markers, cytochrome P450 1A1 (CYP1A1), and glutathione S-transferases Theta 1 (GSTT1) variants in 1,030 self-reported African American mothers. We estimated the African ancestral proportion using the ancestry-informative markers for all 1,030 self-reported African American mothers. We examined the effect of African ancestry and CYP1A1- and GSTT1-smoking interactions on preterm birth cases as a whole and within its subgroups: very preterm birth (gestational age less than 34 weeks); and late preterm birth (gestational age greater than 34 and less than 37 weeks). We applied logistic regression and receiver operating characteristic curve analysis, separately, to evaluate whether African ancestry and CYP1A1- and GSTT1-smoking interactions could make additional contributions to preterm birth beyond epidemiologic factors.
We found significant associations of African ancestry with preterm birth (22% compared with 31%, odds ratio [OR] 1.11, 95% confidence interval [CI] 1.02-1.20) and very preterm birth (23% compared with 33%, OR 1.17, 95% CI 1.03-1.33), but not with late preterm birth (22% compared with 29%, OR 1.06, 95% CI 0.97-1.16). In addition, the receiver operating characteristic curve analysis suggested that African ancestry and CYP1A1- and GSTT1-smoking interactions made substantial contributions to very preterm birth beyond epidemiologic factors.
Our data underscore the importance of simultaneously considering epidemiologic factors, African ancestry, specific gene polymorphisms, and gene-environment interactions to better understand preterm birth racial disparity and to improve our ability to predict preterm birth, especially very preterm birth.
Obstetrics and Gynecology 11/2011; 118(5):1081-9. · 4.73 Impact Factor
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Rajesh Kumar, Hui-Ju Tsai,
Xiumei Hong,
Xin Liu,
Guoying Wang,
Colleen Pearson,
Katherin Ortiz,
Melanie Fu,
Jacqueline A Pongracic,
Howard Bauchner,
Xiaobin Wang
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ABSTRACT: We examined whether the risk of food-allergen sensitization varied according to self-identified race or genetic ancestry.
We studied 1104 children (mean age: 2.7 years) from an urban multiethnic birth cohort. Food sensitization was defined as specific immunoglobulin E (sIgE) levels of ≥ 0.35 kilo-units of allergen (kUA)/L for any of 8 common food allergens. Multivariate logistic regression analyses were used to evaluate the associations of self-identified race and genetic ancestry with food sensitization. Analyses also examined associations with numbers of food sensitizations (0, 1 or 2, and ≥ 3 foods) and with logarithmically transformed allergen sIgE levels.
In this predominantly minority cohort (60.9% black and 22.5% Hispanic), 35.5% of subjects exhibited food sensitizations. In multivariate models, both self-reported black race (odds ratio [OR]: 2.34 [95% confidence interval [CI]: 1.24-4.44]) and African ancestry (in 10% increments; OR: 1.07 [95% CI: 1.02-1.14]) were associated with food sensitization. Self-reported black race (OR: 3.76 [95% CI: 1.09-12.97]) and African ancestry (OR: 1.19 [95% CI: 1.07-1.32]) were associated with a high number (≥ 3) of food sensitizations. African ancestry was associated with increased odds of peanut sIgE levels of ≥ 5 kUA/L (OR: 1.25 [95% CI: 1.01-1.52]). Similar ancestry associations were seen for egg sIgE levels of ≥ 2 kUA/L (OR: 1.13 [95% CI: 1.01-1.27]) and milk sIgE levels of ≥ 5 kUA/L (OR: 1.24 [95% CI: 0.94-1.63]), although findings were not significant for milk.
Black children were more likely to be sensitized to food allergens and were sensitized to more foods. African ancestry was associated with peanut sensitization.
PEDIATRICS 09/2011; 128(4):e821-9. · 4.47 Impact Factor
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Xin Liu,
Guoying Wang,
Xiumei Hong, Hui-Ju Tsai,
Rong Liu,
Shanchun Zhang,
Hongjian Wang,
Colleen Pearson,
Katherin Ortiz,
Deli Wang,
Emmet Hirsch,
Barry Zuckerman,
Xiaobin Wang
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ABSTRACT: There is increasing evidence suggesting that higher intakes of fish or n-3 polyunsaturated fatty acids supplements may decrease the risk of preterm delivery (PTD). We hypothesized that genetic variants of the enzymes critical to fatty acids biosynthesis and metabolism may be associated with PTD. We genotyped 231 potentially functional single nucleotide polymorphisms (SNPs) and tagSNPs in 9 genes (FADS1, FADS2, PTGS1, PTGS2, ALOX5, ALOX5AP, PTGES, PTGES2, and PTGES3) among 1,110 black mothers, including 542 mothers who delivered preterm (<37 weeks gestation) and 568 mothers who delivered full-term babies (≥37 weeks gestation) at Boston Medical Center. After excluding SNPs that are in complete linkage disequilibrium or have lower minor allele frequency (<1%) or call rate (<90%), we examined the association of 206 SNPs with PTD using multiple logistic regression models. We also imputed 190 HapMap SNPs via program MACH and examined their associations with PTD. Finally, we explored gene-level and pathway-level associations with PTD using the adaptive rank truncated product (ARTP) methods. A total of 21 SNPs were associated with PTD (p value ranging from 0.003 to 0.05), including 3 imputed SNPs. Gene-level ARTP statistics indicated that the gene PTGES2 was significantly associated with PTD with a gene-based p value equal to 0.01. No pathway-based association was found. In this large and comprehensive candidate gene study, we found a modest association of genes in fatty acid metabolism pathway with PTD. Further investigation of these gene polymorphisms jointly with fatty acid measures and other genetic factors would help better understand the pathogenesis of PTD.
Human Genetics 08/2011; 131(3):341-51. · 5.07 Impact Factor
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Xiumei Hong,
Guoying Wang,
Xin Liu,
Rajesh Kumar, Hui-Ju Tsai,
Lester Arguelles,
Ke Hao,
Colleen Pearson,
Kathryn Ortiz,
Anthony Bonzagni,
Stephanie Apollon,
Lingling Fu,
Deanna Caruso,
Jacqueline A Pongracic,
Robert Schleimer,
Patrick G Holt,
Howard Bauchner,
Xiaobin Wang
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ABSTRACT: The effect of breast-feeding on the development of allergic disease is uncertain. There are no data that show whether this relationship varies by individual genotypes.
We sought to evaluate the effect of breast-feeding and gene-breast-feeding interactions on food sensitization (FS) in a prospective US birth cohort.
This study included 970 children who were prospectively followed since birth. Breast-feeding history was obtained from a standardized questionnaire interview. FS was defined as a specific IgE level of 0.35 kU(A)/L or greater to any of 8 common food allergens. Eighty-eight potentially functional single nucleotide polymorphisms (SNPs) were genotyped from 18 genes involved in innate immunity or T(H)1/T(H)2 balance. Logistic regression models were used to test the effects of breast-feeding and gene-breast-feeding interactions on FS, with adjustment for pertinent covariates.
Children who were ever breast-fed (n = 739), including exclusively breast-fed children, were at a 1.5 (95% CI, 1.1-2.1; P = .019) times higher risk of FS than never breast-fed children (n = 231). This association was significantly modified by rs425648 in the IL-12 receptor β1 gene (IL12RB1; P for interaction = .0007): breast-feeding increased the risk of FS (odds ratio, 2.0; 95% CI, 1.4-3.1; P = .0005) in children carrying the GG genotype but decreased the risk (odds ratio, 0.6; 95% CI, 0.3-1.4; P = .252) in children carrying the GT/TT genotype. Similar interactions were observed for SNPs in the Toll-like receptor 9 (TLR9; rs352140) and thymic stromal lymphopoietin (TSLP; rs3806933) genes. The interaction between the combined genotypes of the 3 SNPs and breast-feeding on FS was even stronger (P for interaction < 10⁻⁵).
Our data suggest that the effect of breast-feeding on FS was modified by SNPs in the IL12RB1, TLR9, and TSLP genes both individually and jointly. Our findings underscore the importance of considering individual genetic variations in assessing this relationship.
The Journal of allergy and clinical immunology 06/2011; 128(2):374-81.e2. · 9.17 Impact Factor
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Guoying Wang,
Lester Arguelles,
Rong Liu,
Shanchun Zhang,
Wendy J Brickman,
Xiumei Hong, Hui-Ju Tsai,
Binyan Wang,
Houxun Xing,
Zhiping Li,
Xiping Xu,
Xiaobin Wang
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ABSTRACT: We examined the tracking of blood glucose, the development of prediabetes, and estimated their genetic contributions in a prospective, healthy, rural Chinese twin cohort. This report includes 1,766 subjects (998 males, 768 females) aged 6-21 years at baseline who completed a 6-year follow-up study. Oral glucose tolerance test was performed for all subjects at both baseline and follow-up. We found that subjects with low fasting plasma glucose (FPG) or 2 h post-load glucose (PG) levels at baseline tended to remain at the low level at follow-up. Subjects in the top tertile of baseline plasma glucose tended to have a higher risk of developing prediabetes at follow-up compared to the low tertile: in males, 37.6% vs. 27.6% for FPG and 37.2% vs. 25.7% for 2hPG, respectively; in females, 31.0% vs. 15.4% for FPG and 28.9% vs. 15.1% for 2 h PG, respectively. Genetic factors explained 43% and 41% of the variance of FPG, and 72% and 47% for impaired fasting glucose for males and females, respectively; environmental factors substantially contribute to 2hPG status and impaired glucose tolerance. In conclusion, in this cohort of healthy rural Chinese children and adolescents, we demonstrated that both FPG and 2hPG tracked well and was a strong predictor of prediabetes. The high proportion of children with top tertile of blood glucose progressed to prediabetes, and the incidence of prediabetes has a male predominance. Genetic factors play more important role in fasting than postload status, most of which was explained by unique environmental factors.
PLoS ONE 01/2011; 6(12):e28573. · 4.09 Impact Factor
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ABSTRACT: A previous study has reported that the Ile227 and Ala357 genetic variants of human urea transporter-2 (HUT2) were associated with blood pressure in males in Asian population. In this study, we aimed to investigate five known HUT2 genetic variants with metabolic syndrome (MetS) and its related traits in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) study cohort.
Five HUT2 single nucleotide polymorphisms (SNPs) were selected and genotyped among 1791 subjects in the SAPPHIRe study cohort. We first computed allele frequency and performed Hardy-Weinberg equilibrium (HWE) test in controls for each SNP. Next, we tested genotype associations with metabolic syndrome using multiple generalized estimating equations (GEE) models with covariate adjustment. Furthermore, multi-marker and multi-trait association tests were carried out using FBAT program. To account for multiple testing, Bonferroni correction was applied in this study.
Among those 5 HUT2 SNPs, SNPs 1, 2 and 3 were significantly associated with MetS in the total sample and females, separately (9×10(-4)≤p≤0.04), but only the association between SNP 1 and MetS in females remained statistically significant after Bonferroni correction. When testing 5 SNPs simultaneously, significant associations were found with triglycerides (TG) (p=0.04). Likewise, significant multi-trait association (combining the data of waist circumference, TG, high density lipoprotein (HDL) cholesterol and fasting glucose together) was found with SNP 2 (p=0.04), but both results of multi-maker and multi-trait associations did not remain significant after multiple testing correction.
The results have provided evidence that the HUT2 gene may play a certain role in developing MetS and its related traits in Asian population. Further investigation of the HUT2 gene influencing MetS and its related traits will be warranted.
Clinica chimica acta; international journal of clinical chemistry 12/2010; 411(23-24):2009-13. · 2.54 Impact Factor
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Xiumei Hong, Hui-Ju Tsai,
Xin Liu,
Lester Arguelles,
Rajesh Kumar,
Guoying Wang,
Nataliya Kuptsova-Clarkson,
Colleen Pearson,
Kathryn Ortiz,
Anthony Bonzagni,
Stephanie Apollon,
Lingling Fu,
Jacqueline A Pongracic,
Robert Schleimer,
Patrick G Holt,
Howard Bauchner,
Xiaobin Wang
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ABSTRACT: Elucidation of early life factors is critical to understand the development of allergic diseases, especially those manifesting in early life such as food allergies and atopic dermatitis. Cord blood IgE (CBIgE) is a recognized risk factor for the subsequent development of allergic diseases. In contrast with numerous genetic studies of total serum IgE in children and adults, limited genetic studies on CBIgE have been conducted.
To test the associations between functional or tagging single nucleotide polymorphisms (SNPs) in genes involved in the T(H)1/T(H)2 pathway and CBIgE in a large US inner-city birth cohort.
CBIgE, measured by Phadia ImmnunoCAP, was analyzed as a continuous and a binary variable. The association of each SNP with the 2 outcomes was tested using tobit and logistic regression models, respectively, with adjustment for pertinent covariates, ancestral proportion, and multiple testing. Ethnic heterogeneity and gene-gene interactions were also explored.
Three SNPs (rs1800925, rs2069743, and rs1295686) in the IL13 gene were significantly associated with CBIgE concentration (P ≤ 6 × 10(-4), FDR-corrected P < .05). These SNPs jointly influenced CBIgE in a dose-response manner (P for trend = 9 × 10(-8)). Significant associations also were observed for SNPs in the IL-13 receptor α1 (rs5956080) and signal transducer and activator of transcription 6 (rs11172106) genes. Ethnicity-specific genetic effects were observed for SNPs in the IL5 and GATA3 genes. Several gene-gene interactions (including IL13-IL4 receptor and IL13-signal transducer and activator of transcription 6 interactions) were detected in relation to CBIgE.
Our data demonstrated that multiple SNPs were individually and jointly associated with CBIgE, with evidence of gene-gene interactions and ethnic heterogeneity. These findings suggest that genetic regulation of IgE may begin in utero.
The Journal of allergy and clinical immunology 11/2010; 126(5):1059-67, 1067.e1. · 9.17 Impact Factor
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Shanchun Zhang,
Xin Liu,
Jonathan Necheles, Hui-Ju Tsai,
Guoying Wang,
Binyan Wang,
Houxun Xing,
Zhiping Li,
Xue Liu,
Tonghua Zang,
Xiping Xu,
Xiaobin Wang
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ABSTRACT: We conducted cross-sectional and longitudinal twin analysis to explore genetic and environmental contribution to serum lipid tracking during childhood and adolescence. The study sample was part of a population-based twin cohort that was recruited in the rural areas of the Anhui Province of China. The baseline recruitment of twins was carried out from 1998 through 2000 and the follow-up from 2005 through 2007. Serum lipids showed significant tracking during childhood and adolescence. Participants with lipids at the highest tertile at the baseline tended to remain high at follow-up across ages and Tanner stages, whereas subjects with lipids at the lowest tertile at the baseline tended to remain low at follow-up. Using twin modeling, we showed that genetic and environmental factors contributed to individual variations in lipid levels and tracking from the baseline to the follow-up visit. The estimated tracking correlations for total cholesterol, triglyceride, and LDL cholesterol were in the range of 0.25-0.53 and were predominantly influenced by genetic factors. In contrast, the phenotypic tracking of HDL cholesterol was influenced by both genetic and environmental factors. Our study underscores the importance of considering both environmental and genetic factors in studying the etiology of dyslipidemia.
Pediatric Research 10/2010; 68(4):316-22. · 2.70 Impact Factor
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American journal of obstetrics and gynecology 02/2010; · 3.28 Impact Factor
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Xiumei Hong,
Lester M Arguelles, Hui-Ju Tsai,
Shanchun Zhang,
Guoying Wang,
Binyan Wang,
Xue Liu,
Zhiping Li,
Genfu Tang,
Houxun Xing,
Xiping Xu,
Xiaobin Wang
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ABSTRACT: Adipokines have been linked to bone phenotypes recently, but with conflicting results. Few such studies have been conducted in adolescents.
The aim of the study was to examine the associations of adiponectin and leptin with multiple bone phenotypes in Chinese adolescents and estimate the genetic contribution to these associations.
This was a cross-sectional study conducted in rural China.
A total of 675 males and 575 females aged 13-21 yr were included.
Fat mass (FM), lean mass (LM), bone area (BA), bone mineral content (BMC), cross-sectional area (CSA), and section modulus (SM) were measured by dual-energy x-ray absorptiometry. Plasma adipokine concentration was determined using sandwich immunoassays.
Adiponectin was inversely associated with all BMCs in males (P < 0.01), but not in females, after adjusting for LM, body weight, or BMI singly, or for LM and FM simultaneously. No such relationships were observed for CSA or SM in both genders. Leptin was inversely associated with all BAs, total-hip BMC, CSA, and SM in both genders, when adjusting for body weight or BMI. These associations, except for whole-body BA and lumbar spine BA in females, disappeared when simultaneously adjusting for LM and FM. By Cholesky decomposition models using twin design, significant genetic correlations were detected between adiponectin and total-hip BMC in males and between leptin and total-hip BMC in both genders.
We demonstrated that adiponectin and leptin were inversely associated with adolescent bone phenotypes but showed differential associations by gender, type of bone phenotypes, and adjustment of FM. This study also suggested that adipokines and bone phenotypes may share a common set of genes.
The Journal of clinical endocrinology and metabolism 02/2010; 95(4):1644-52. · 6.50 Impact Factor
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Xiumei Hong,
Lester M Arguelles,
Xin Liu, Hui-Ju Tsai,
Yi-Hsiang Hsu,
Binyan Wang,
Shanchun Zhang,
Zhiping Li,
Gengfu Tang,
Xue Liu,
Jianhua Yang,
Xiping Xu,
Craig Langman,
Xiaobin Wang
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ABSTRACT: This study was an attempt to examine the phenotypic, genetic, and environmental correlations between percent fat mass (PFM) and bone parameters, especially hip geometry, among 786 males and 618 females aged 13 to 21 years from a Chinese twin cohort. PFM, bone area (BA), bone mineral content (BMC), cross-sectional area (CSA), and section modulus (SM) were obtained by dual-energy X-ray absorptiometry. Multiple linear regression models were used to assess the PFM-bone relationships. A structural equation model for twin design was used to estimate genetic/environmental influences on individual phenotype and phenotypic correlations. After controlling for body weight and other pertinent covariates, we observed inverse associations between PFM and bone parameters: Compared with the lowest age- and gender-specific tertile of PFM, males in the highest tertile of PFM had lower measures of whole-body-less-head BA (WB-BA), lumbar spine BA (L(2)-L(4)-BA), total-hip BA (TH-BA), total-hip BMC, CSA, and SM (p < .005 for all, adjusted p < .05). Similar inverse associations were observed in females for all the preceding parameters except WB-BA and L2-L(4)-BA. These associations did not vary significantly by Tanner stages. In both genders, the estimated heritabilities were 80% to 86% for BMC, 67% to 80% for BA, 74% to 77% for CSA, and 64% for SM. Both shared genetics and environmental factors contributed to the inverse PFM-bone correlations. We conclude that in this sample of relatively lean Chinese adolescents, at a given body weight, PFM is inversely associated with BA, BMC, and hip geometry in both genders, and such associations are attributed to both shared genetic and environmental factors.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2010; 25(7):1544-54. · 6.04 Impact Factor
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ABSTRACT: Food allergy, a growing clinical and public health problem in the United States and worldwide, is likely determined by multiple environmental and genetic factors. The purpose of this review is to summarize recent advances in food allergy genetic research.
There is compelling evidence that genetic factors may play a role in food allergy. However, the specific genetic loci that may modulate individual risk of food allergy remain to be identified. To date, only a limited number of candidate gene association studies of food allergy have been reported. Polymorphism(s) in nine genes have been associated with the incidence of food allergy or food allergy severity in at least one study. But most of these findings remain to be replicated in independent populations. In contrast, there are considerable advances in genetics of other allergic diseases such as asthma and atopic dermatitis. Although asthma and atopic dermatitis often coexist with food allergy, the relevance of their candidate genes to food allergy remains to be evaluated.
Genetics in food allergy is a promising research area but is still in its infancy. More studies are needed to dissect susceptible genes of food allergy. A genome-wide association approach may serve as a powerful tool to identify novel genes related to food allergy. Furthermore, the role of gene-environment interaction, gene-gene interaction, and epigenetics in food allergy remains largely unexplored. Given the complex nature of food allergy, future studies need to integrate environment, genomics, and epigenomics in order to better understand the multifaceted etiology and biological mechanisms of food allergy.
Current opinion in pediatrics 10/2009; 21(6):770-6. · 2.01 Impact Factor
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Shanchun Zhang,
Xin Liu,
Wendy J Brickman,
Katherine Kaufer Christoffel,
Donald Zimmerman, Hui-Ju Tsai,
Guoying Wang,
Binyan Wang,
Zhiping Li,
Gengfu Tang,
Xue Liu,
Jianhua Yang,
Xiping Xu,
Xiaobin Wang
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ABSTRACT: There is evidence that leptin is involved in the etiology of obesity-related cardiovascular disease in adults. This raises the question of whether leptin levels in adolescence are indicative of adiposity-related cardiovascular risk.
This study investigated gender-specific patterns of plasma leptin during adolescence, assessed which adiposity measurements are most strongly associated with plasma leptin, and estimated to what degree leptin-adiposity associations are influenced by genetic factors.
Plasma leptin concentrations were determined using a sandwich immunoassay. Associations between plasma leptin and several adiposity measurements were examined using generalized estimating equations. Genetic contribution to leptin-adiposity association was estimated by Cholesky decomposition models using twin design.
Plasma leptin levels were higher in females than males at all Tanner stages. In females, body mass index, waist circumference, fat mass index (FMI), and percentage body fat (%BF) had similar associations with leptin levels. In males, %BF and FMI were more strongly associated with leptin levels than body mass index and waist circumference. In both males and females, percentage trunk fat had the weakest association with leptin among the five adiposity measures. Shared genetic factors account for more than 80% of the phenotypic correlation between %BF and leptin.
We found gender differences in leptin levels and leptin-adiposity associations. In both genders, leptin levels were strongly associated with %BF and FMI, particularly in males. Shared genetic factors contributed largely to the phenotypic correlation between leptin and %BF. Our findings underscored the importance of further investigation of leptin as a biomarker of adiposity in adolescents.
The Journal of clinical endocrinology and metabolism 08/2009; 94(9):3497-504. · 6.50 Impact Factor
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ABSTRACT: In the United States, the rate of preterm delivery (PTD) is higher in African Americans (17.8%) than non-Hispanic whites (11.5%). Such disparity cannot be fully explained by differences in socioenvironmental factors.
We genotyped 812 mothers in a case-control PTD study at Boston Medical Center who self-reported their ethnicity as "black." Regression analysis and Wilcoxon rank-sum test were applied to evaluate ancestral distribution and the association between genetic ancestry and PTD-related traits, as well as the potential confounding effect of population stratification.
The estimated African ancestral proportion was 0.90 +/- 0.13. We found significant associations of ancestral proportion with PTD as a whole and PTD subgrouped by the presence of maternal hypertensive disorders. We did not observe significant confounding as a result of population stratification in this case-control PTD study.
Our data underline the need for more intensive investigation of genetic admixture in African Americans to identify novel susceptibility genes of PTD.
American journal of obstetrics and gynecology 06/2009; 201(1):94.e1-10. · 3.28 Impact Factor
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Shanchun Zhang,
Xin Liu,
Yunxian Yu,
Xiumei Hong,
Katherine K Christoffel,
Binyan Wang, Hui-Ju Tsai,
Zhiping Li,
Xue Liu,
Genfu Tang,
Houxun Xing,
Wendy J Brickman,
Donald Zimmerman,
Xiping Xu,
Xiaobin Wang
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ABSTRACT: The increasing prevalence of metabolic syndrome (MS) poses a serious public-health problem worldwide. Effective prevention and intervention require improved understanding of the factors that contribute to MS. We analyzed data on a large twin cohort to estimate genetic and environmental contributions to MS and to major MS components and their intercorrelations: waist circumference (WC), systolic (SBP) and diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglycerides (TGs), and high-density lipoprotein-cholesterol (HDL-C). We applied structural equation modeling to determine genetic and environmental structure of MS and its major components, using 1,617 adult female twin pairs recruited from rural China. The heritability estimate for MS was 0.42 (95% confidence interval (CI): 0.00-0.83) in this sample with low MS prevalence (4.4%). For MS components, heritability estimates were statistically significant and ranged from 0.13 to 0.64 highest for WC, followed by TG, SBP, DBP, HDL-C, and FPG. HDL-C was mainly influenced by common environmental factors (0.62, 95% CI: 0.58-0.62), whereas the other five MS components were largely influenced by unique environmental factors (0.32-0.44). Bivariate Cholesky decomposition analysis indicated that the clinical clustering of MS components may be explained by shared genetic and/or environmental factors. Our study underscores the importance of examining MS components as intercorrelated traits, and to carefully consider environmental and genetic factors in studying MS etiology.
Obesity 05/2009; 17(8):1581-7. · 4.28 Impact Factor
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ABSTRACT: Factor V (F5) genetic variants and maternal smoking during pregnancy individually has been associated with increased risk of preterm delivery (PTD). We hypothesize that F5 gene and maternal smoking may synergistically increase the risk of PTD. Three single nucleotide polymorphisms (SNPs) in F5 gene (rs6019, rs2213869 and rs6022) were genotyped in 542 mothers with PTD and 1,141 mothers with term deliveries at the Boston Medical Center. The individual and interactive effects of F5 SNPs and maternal smoking on PTD and gestational age were examined, respectively. The results suggested that maternal smoking, three F5 SNPs and F5 haplotype were individually associated with PTD and gestational age. More importantly, we found significant interactions between the two F5 SNPs (rs6019 and rs6022) and maternal smoking on PTD and gestational age. Compared with non-smoking mothers carrying rs6019 GG genotype, persistently smoking mothers carrying genotypes GC or CC were associated with significantly increased risk of PTD (OR(95% CI): 2.1(1.2-3.6) for GC; 5.7(2.1-15.0) for CC; p-interaction = 0.02). A significant interaction was also observed for gestational age. Similar pattern of interactions was found between rs6022 and maternal smoking on PTD. In summary, our data indicated that F5 gene variants and maternal smoking may synergistically increase the risk of PTD.
Human Genetics 12/2008; 124(6):659-68. · 5.07 Impact Factor
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Xiumei Hong, Hui-Ju Tsai,
Xin Liu,
Zhiping Li,
Xue Liu,
Genfu Tang,
Houxun Xing,
Jianhua Yang,
Binyan Wang,
Yan Feng,
Xin Xu,
Xiping Xu,
Xiaobin Wang
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ABSTRACT: A number of genome-wide scans of stature have been reported previously, but with inconsistent results. The inconsistency may be partly due to differential population characteristics and gender- and/or age-specific effects on this trait.
This study aimed to identify the quantitative trait loci (QTLs) underlying the variation of stature in Chinese population, and to evaluate age- and gender-specific linkage for stature.
We conducted a large-scale, genome-wide linkage scan using the data from three independent samples (a total of 7112 subjects from 1811 pedigrees) enrolled from the same geographical region in China. Linkage analyses were performed in the pooled samples and in subgroups defined by age (<or=25 vs. >25 yr), gender, or both, using the model-free regression method implemented in MERLIN-REGRESS.
The strongest linkage signal was obtained on 17q24 (LOD=3.82) in the pooled samples. Age-specific analysis revealed two additional significant QTLs on 13q34 and 18p11.3 among subjects 25 yr or younger. In gender-specific analyses, males showed suggestive QTLs on 12q21 (LOD=2.31) and 17q22 (LOD=2.60), and females showed a suggestive QTL on 13q31.1 (LOD=2.68). Age- and gender-specific linkage analyses suggested that males older than 25 yr contributed more signals to QTLs on 12q21 and 17q22, with a LOD score of 3.00 and 2.26, respectively, whereas females older than 25 yr presented a suggestive QTL on 8q24.3 (LOD=2.57).
Our study identified a strong linkage of chromosome 17q24 to stature in this Chinese population, and indicated that it may be informative to consider differential age and gender effects in the genetic dissection of stature.
Journal of Clinical Endocrinology & Metabolism 08/2008; 93(11):4511-8. · 6.50 Impact Factor
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Hui-Ju Tsai,
Xin Liu,
Karen Mestan,
Yunxian Yu,
Shanchun Zhang,
Yaping Fang,
Colleen Pearson,
Katherin Ortiz,
Barry Zuckerman,
Howard Bauchner,
Sandra Cerda,
Phillip G Stubblefield,
Xiping Xu,
Xiaobin Wang
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ABSTRACT: Preterm delivery (PTD, <37 weeks of gestation) is a significant clinical and public health problem. Previously, we reported that maternal smoking and metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 synergistically increase the risk of low birth weight. This study investigates the relationship between maternal smoking and metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 with preterm delivery (PTD) as a whole and preterm subgroups. This case-control study included 1,749 multi-ethnic mothers (571 with PTD and 1,178 controls) enrolled at Boston Medical Center. After adjusting covariates, regression analyses were performed to identify individual and joint associations of maternal smoking, two functional variants of CYP1A1 and GSTT1 with PTD. We observed a moderate effect of maternal smoking on PTD (OR = 1.6; 95% CI: 1.1-2.2). We found that compared to non-smoking mothers with low-risk genotypes, there was a significant joint association of maternal smoking, CYP1A1 (Aa/aa) and GSTT1 (absent) genotypes with gestational age (beta = -3.37; SE = 0.86; P = 9 x 10(-5)) and with PTD (OR = 5.8; 95% CI: 2.0-21.1), respectively. Such joint association was particularly strong in certain preterm subgroups, including spontaneous PTD (OR = 8.3; 95% CI: 2.7-30.6), PTD < 32 weeks (OR = 11.1; 95% CI: 2.9-47.7), and PTD accompanied by histologic chorioamnionitis (OR = 15.6; 95% CI: 4.1-76.7). Similar patterns were observed across ethnic groups. Taken together, maternal smoking significantly increased the risk of PTD among women with high-risk CYP1A1 and GSTT1 genotypes. Such joint associations were strongest among PTD accompanied by histologic chorioamnionitis.
Human Genetics 06/2008; 123(4):359-69. · 5.07 Impact Factor
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ABSTRACT: Type 2 diabetes mellitus (T2DM) is a common complex phenotype that by the year 2010 is predicted to affect 221 million people globally. In the present study we performed a genome-wide linkage scan using the allele-sharing statistic Sall implemented in Allegro and a novel two-dimensional genome-wide strategy implemented in Merloc that searches for pairwise interaction between genetic markers located on different chromosomes linked to T2DM. In addition, we used a robust score statistic from the newly developed QTL-ALL software to search for linkage to variation in adult height. The strategies were applied to a study sample consisting of 238 sib-pairs affected with T2DM from American Samoa. We did not detect any genome-wide significant susceptibility loci for T2DM. However, our two-dimensional linkage investigation detected several loci pairs of interest, including 11q22 and 21q21, 9q21 and 11q22, 1p22-p21 and 4p15, and 4p15 and 15q11-q14, with a two-loci maximum LOD score (MLS) greater than 2.00. Most detected individual loci have previously been identified as susceptibility loci for diabetes-related traits. Our two-dimensional linkage results may facilitate the selection of potential candidate genes and molecular pathways for further diabetes studies because these results, besides providing candidate loci, also demonstrate that polygenic effects may play an important role in T2DM. Linkage was detected (p value of 0.005) for variation in adult height on chromosome 9q31, which was reported previously in other populations. Our finding suggests that the 9q31 region may be a strong quantitative trait locus for adult height, which is likely to be of importance across populations.
Human Biology 05/2008; 80(2):99-123. · 1.31 Impact Factor
