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1.
Ruyang Zhang Yang Zhao Minjie Chu Amar Mehta Yongyue Wei Yao Liu Pengcheng Xun Jianling Bai Hao Yu Li Su Hongxi Zhang Zhibin Hu Hongbing Shen Feng Chen David C. Christiani 《PloS one》2013,8(3)
Background
Occupational exposure to endotoxin is associated with decrements in pulmonary function, but how much variation in this association is explained by genetic variants is not well understood.Objective
We aimed to identify single nucleotide polymorphisms (SNPs) that are associated with the rate of forced expiratory volume in one second (FEV1) decline by a large scale genetic association study in newly-hired healthy young female cotton textile workers.Methods
DNA samples were genotyped using the Illumina Human CVD BeadChip. Change rate in FEV1 was modeled as a function of each SNP genotype in linear regression model with covariate adjustment. We controlled the type 1 error in study-wide level by permutation method. The false discovery rate (FDR) and the family-wise error rate (FWER) were set to be 0.10 and 0.15 respectively.Results
Two SNPs were found to be significant (P<6.29×10−5), including rs1910047 (P = 3.07×10−5, FDR = 0.0778) and rs9469089 (P = 6.19×10−5, FDR = 0.0967), as well as other eight suggestive (P<5×10−4) associated SNPs. Gene-gene and gene-environment interactions were also observed, such as rs1910047 and rs1049970 (P = 0.0418, FDR = 0.0895); rs9469089 and age (P = 0.0161, FDR = 0.0264). Genetic risk score analysis showed that the more risk loci the subjects carried, the larger the rate of FEV1 decline occurred (P trend = 3.01×10−18). However, the association was different among age subgroups (P = 7.11×10−6) and endotoxin subgroups (P = 1.08×10−2). Functional network analysis illustrates potential biological connections of all interacted genes.Conclusions
Genetic variants together with environmental factors interact to affect the rate of FEV1 decline in cotton textile workers. 相似文献2.
3.
Jie Wen Tina R?nn Anders Olsson Zhen Yang Bin Lu Yieping Du Leif Groop Charlotte Ling Renming Hu 《PloS one》2010,5(2)
Background
Recent genome-wide association studies (GWASs) have reported several genetic variants to be reproducibly associated with type 2 diabetes. Additional variants have also been detected from a metaanalysis of three GWASs, performed in populations of European ancestry. In the present study, we evaluated the influence of 17 genetic variants from 15 candidate loci, identified in type 2 diabetes GWASs and the metaanalysis, in a Han Chinese cohort.Methodology/Principal Findings
Selected type 2 diabetes–associated genetic variants were genotyped in 1,165 type 2 diabetic patients and 1,136 normoglycemic control individuals of Southern Han Chinese ancestry. The OR for risk of developing type 2 diabetes was calculated using a logistic regression model adjusted for age, sex, and BMI. Genotype-phenotype associations were tested using a multivariate linear regression model. Genetic variants in CDKN2A/B, CDKAL1, TCF7L2, TCF2, MC4R, and PPARG showed a nominal association with type 2 diabetes (P≤0.05), of whom the three first would stand correction for multiple testing: CDKN2A/B rs10811661, OR: 1.26 (1.12–1.43) P = 1.8*10−4; CDKAL1 rs10946398, OR: 1.23 (1.09–1.39); P = 7.1*10−4, and TCF7L2 rs7903146, OR: 1.61 (1.19–2.18) P = 2.3 * 10−3. Only nominal phenotype associations were observed, notably for rs8050136 in FTO and fasting plasma glucose (P = 0.002), postprandial plasma glucose (P = 0.002), and fasting C-peptide levels (P = 0.006) in the diabetic patients, and with BMI in controls (P = 0.033).Conclusions/Significance
We have identified significant association between variants in CDKN2A/B, CDKAL1 and TCF7L2, and type 2 diabetes in a Han Chinese cohort, indicating these genes as strong candidates conferring susceptibility to type 2 diabetes across different ethnicities. 相似文献4.
Jaakko T. Leinonen Ida Surakka Aki S. Havulinna Johannes Kettunen Riitta Luoto Veikko Salomaa Elisabeth Widén 《PloS one》2012,7(11)
Context
Pubertal timing is under strong genetic control and its early onset associates with several adverse health outcomes in adulthood, including obesity, type 2 diabetes and cardiovascular disease. Recent data indicate strong association between pubertal timing and genetic variants near LIN28B, but it is currently unknown whether the gene contributes to the association between puberty and adult disease.Objective
To elucidate the putative genetic link between early puberty and adult disease risk, we examined the association of two genetic variants near LIN28B with adult body size and metabolic profiles in randomly ascertained adult Finnish males and females.Methods
Two single nucleotide polymorphisms (SNPs), rs7759938, the lead SNP previously associated with pubertal timing and height, and rs314279, previously also associated with menarcheal age but only partially correlated with rs7759938 (r2 = 0.30), were genotyped in 26,636 study subjects participating in the Finnish population survey FINRISK. Marker associations with adult height, weight, body mass index (BMI), hip and waist circumference, blood glucose, serum insulin and lipid/lipoprotein levels were determined by linear regression analyses.Results
Both rs7759938 and rs314279 associated with adult height in both sexes (p = 2×10−6 and p = 0.001). Furthermore, rs314279 associated with increased weight in females (p = 0.001). Conditioned analyses including both SNPs in the regression model verified that rs314279 independently associates with adult female weight, BMI and hip circumference (p<0.005). Neither SNP associated with glucose, lipid, or lipoprotein levels.Conclusion
Genetic variants near the puberty-associated gene LIN28B associate with adult weight and body shape in females, suggesting that the gene may tag molecular pathways influencing adult adiposity-related traits. 相似文献5.
6.
Fumihiko Takeuchi Masato Isono Tomohiro Katsuya Mitsuhiro Yokota Ken Yamamoto Toru Nabika Kazuro Shimokawa Eitaro Nakashima Takao Sugiyama Hiromi Rakugi Shuhei Yamaguchi Toshio Ogihara Yukio Yamori Norihiro Kato 《PloS one》2012,7(9)
Background/Objective
In Japanese populations, we performed a replication study of genetic loci previously identified in European-descent populations as being associated with lipid levels and risk of coronary artery disease (CAD).Methods
We genotyped 48 single nucleotide polymorphisms (SNPs) from 22 candidate loci that had previously been identified by genome-wide association (GWA) meta-analyses for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and/or triglycerides in Europeans. We selected 22 loci with 2 parallel tracks from 95 reported loci: 16 significant loci (p<1×10−30 in Europeans) and 6 other loci including those with suggestive evidence of lipid associations in 1292 GWA-scanned Japanese samples. Genotyping was done in 4990 general population samples, and 1347 CAD cases and 1337 controls. For 9 SNPs, we further examined CAD associations in an additional panel of 3052 CAD cases and 6335 controls.Principal Findings
Significant lipid associations (one-tailed p<0.05) were replicated for 18 of 22 loci in Japanese samples, with significant inter-ethnic heterogeneity at 4 loci–APOB, APOE-C1, CETP, and APOA5–and allelic heterogeneity. The strongest association was detected at APOE rs7412 for LDL-C (p = 1.3×10−41), CETP rs3764261 for HDL-C (p = 5.2×10−24), and APOA5 rs662799 for triglycerides (p = 5.8×10−54). CAD association was replicated and/or verified for 4 loci: SORT1 rs611917 (p = 1.7×10−8), APOA5 rs662799 (p = 0.0014), LDLR rs1433099 (p = 2.1×10−7), and APOE rs7412 (p = 6.1×10−13).Conclusions
Our results confirm that most of the tested lipid loci are associated with lipid traits in the Japanese, further indicating that in genetic susceptibility to lipid levels and CAD, the related metabolic pathways are largely common across the populations, while causal variants at individual loci can be population-specific. 相似文献7.
Claudia Ha Ting Tam Janice Sin Ka Ho Ying Wang Heung Man Lee Vincent Kwok Lim Lam Soren Germer Mitchell Martin Wing Yee So Ronald Ching Wan Ma Juliana Chung Ngor Chan Maggie Chor Yin Ng 《PloS one》2010,5(7)
Background
Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts.Methodology/Principal Findings
Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6×10−5) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P = 0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P = 2.9×10−9) and reduced HOMA-B (P = 1.1×10−3). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG.Conclusions/Significance
Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. 相似文献8.
Om Prakash Dwivedi Rubina Tabassum Ganesh Chauhan Saurabh Ghosh Raman K. Marwaha Nikhil Tandon Dwaipayan Bharadwaj 《PloS one》2012,7(10)
Background
FTO variants are robustly associated with obesity and related traits in many population and shown to have variable impact during life course. Although studies have shown association of FTO variants with adiposity in adult Indian, its association in Indian children is yet to be confirmed.Methods
Here we examined association of FTO variants (rs9939609 and rs8050136) with obesity and related anthropometric and biochemical traits in 3,126 Indian children (aged 11–17 years) including 2,230 normal-weight and 896 over-weight/obese children. We also compared effects observed in the present study with that observed in previous studies on South Asian adults and children of other ethnic groups.Results
The variant rs9939609 showed significant association with risk of obesity [OR = 1.21, P = 2.5×10−3] and its measures BMI, weight, waist circumference and hip circumference [β range = 0.11 to 0.14 Z-score units; P range = 1.3×10−4 to 1.6×10−7] in children. The observed effect sizes in Indian children were similar to those reported for European children. Variant rs9939609 explained 0.88% of BMI variance in Indian children. The effect sizes of rs9939609 on BMI and WC were ∼2 fold higher in children than adults. Interestingly rs9939609 was also associated with serum levels of thyroid stimulating hormone (TSH) [β = 0.10 Z-score, P = 5.8×10−3]. The other variant rs8050136 was in strong linkage disequilibrium with rs9939609 (r2 = 0.97) and provided similar association results.Conclusion
The study provides first report of association of FTO variants with obesity and related anthropometric traits in Indian children with higher impact in children compared to adults. We also demonstrated association of FTO variant with serum levels of TSH, indicating putative influence of FTO in hypothalamic-pituitary-thyroid axis. 相似文献9.
Ju-Sheng Zheng Donna K. Arnett Laurence D. Parnell Yu-Chi Lee Yiyi Ma Caren E. Smith Kris Richardson Duo Li Ingrid B. Borecki Katherine L. Tucker José M. Ordovás Chao-Qiang Lai 《PloS one》2013,8(6)
Background
Neighboring genes PIK3CA and KCNMB3 are both important for insulin signaling and β-cell function, but their associations with glucose-related traits are unclear.Objective
The objective was to examine associations of PIK3CA-KCNMB3 variants with glucose-related traits and potential interaction with dietary fat.Design
We first investigated genetic associations and their modulation by dietary fat in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 820). Nine single-nucleotide polymorphisms (SNPs) were selected for analysis, covering more than 80% of the SNPs in the region. We then sought to replicate the findings in the Boston Puerto Rican Health Study (BPRHS) (n = 844).Results
For KCNMB3 missense mutation rs7645550, meta-analysis indicated that homeostasis model assessment of insulin resistance (HOMA-IR) was significantly lower in minor allele T homozygotes compared with major allele C carriers (pooled P-value = 0.004); for another SNP rs1183319, which is in moderate LD with rs7645550, minor allele G carriers had higher HOMA-IR compared with non-carriers in both populations (pooled P-value = 0.028). In GOLDN, rs7645550 T allele homozygotes had lower HOMA-IR only when dietary n-3: n-6 PUFA ratio was low (≤0.11, P = 0.001), but not when it was high (>0.11, P-interaction = 0.033). Similar interaction was observed between rs1183319 and n-3: n-6 PUFA ratio on HOMA-IR (P-interaction = 0.001) in GOLDN. Variance contribution analyses in GOLDN confirmed the genetic association and gene-diet interaction. In BPRHS, dietary n-3: n-6 PUFA ratio significantly modulated the association between rs1183319 and HbA1c (P-interaction = 0.034).Conclusion
PIK3CA-KCNMB3 variants are associated with insulin resistance in populations of different ancestries, and are modified by dietary PUFA. 相似文献10.
Zhenzhen Qin Yanru Wang Songyu Cao Yisha He Hongxia Ma Guangfu Jin Zhibin Hu Xiaoxiang Guan Hongbing Shen 《PloS one》2013,8(6)
Background
A recent genome-wide association study (GWAS) has identified three new breast cancer susceptibility loci at 12p11, 12q24 and 21q21 in populations of European descent. However, because of the genetic heterogeneity, it is largely unknown for the role of these loci in the breast cancer susceptibility in the populations of non-European descent.Methodology/Principal Findings
Here, we genotyped three variants (rs10771399 at 12p11, rs1292011 at 12q24 and rs2823093 at 21q21) in an independent case–control study with a total of 1792 breast cancer cases and 1867 cancer-free controls in a Chinese population. We found that rs10771399 and rs1292011 were significantly associated with risk of breast cancer with per-allele odds ratios (ORs) of 0.85 (95% confidence interval (CI): 0.76–0.96; P = 0.010) and 0.84 (95% CI: 0.76–0.95; P = 4.50×10−3), respectively, which was consistent with those reported in populations of European descent. Similar effects were observed between ER/PR positive and negative breast cancer for both loci. However, we did not found significant association between rs2823093 and breast cancer risk (OR = 0.97, 95%CI = 0.76–1.24; P = 0.795).Conclusions/Significance
Our results indicate that genetic variants at 12p11 and 12q24 may also play an important role in breast cancer development in Chinese women. 相似文献11.
Hongyan Chen Bing Sun Yingjie Zhao Xiao Song Weiwei Fan Keke Zhou Liangfu Zhou Ying Mao Daru Lu 《PloS one》2012,7(12)
Background
A single nucleotide polymorphism (SNP) at locus 11q23.3 (rs498872) in the near 5′-UTR of the PHLDB1 gene was recently implicated as a risk factor for gliomas in a genome-wide association study, and this involvement was confirmed in three additional studies.Methodology/Principal Findings
To identify possible causal variants in the region, the authors genotyped 15 tagging SNPs in the 200 kb genomic region at 11q23.3 locus in a Chinese Han population-based case-control study with 983 cases and 1024 controls. We found evidence for an association between two independent loci (both the PHLDB1 and the ACRN1 genes) and a predisposition for gliomas. Among the multiple significant SNPs in the PHLDB1 gene region, the rs17749 SNP was the most significant [P = 1.31×10−6 in a recessive genetic model]. Additionally, two novel SNPs (rs2236661 and rs494560) that were independent of rs17749 were significantly associated with glioma risk in a recessive genetic model [P = 1.31×10−5 and P = 3.32×10−5, respectively]. The second novel locus was within the ARCN1 gene, and it was associated with a significantly reduced risk for glioma.Conclusions/Significance
Our data strongly support PHLDB1 as a susceptibility gene for glioma, also shedding light on a new potentially candidate gene, ARCN1. 相似文献12.
Bo Zhang Han Zhao Tao Li Xuan Gao Qin Gao Rong Tang Jiangtao Zhang Zi-Jiang Chen 《PloS one》2012,7(10)
Background
Previous genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in Han Chinese population has found that SNPs in LPP gene were nominally significant in PCOS patients (P around 10E-05). Replication of the GWAS was applied to further confirm the relationship between LPP gene and PCOS.Methods
Three polymorphisms of LPP gene (rs715790, rs4449306, rs6782041) were selected and replicated in additional 1132 PCOS cases and 1142 controls. Genotyping of LPP gene was carried out by Taqman-MGB method.Results
In rs715790, the allele frequency is significantly different between the PCOS group and the control group. Meta-analysis showed that the allele frequencies of the three SNPs rs715790 (Pmeta = 1.89E-05, OR = 1.23), rs4449306 (Pmeta = 3.0E-04, OR = 1.10), rs6782041 (Pmeta = 2.0E-04, OR = 1.09), were significantly different between PCOS cases and controls.Conclusions
Our results suggest that LPP gene might be a novel candidate for PCOS. 相似文献13.
Wenjing Ou Xin Liu Yue Shen Jiana Li Lingbin He Yuan Yuan Xuerui Tan Lisheng Liu Jingbo Zhao Xingyu Wang 《PloS one》2014,9(8)
Background
Contribution of cardiovascular disease related genetic risk factors for stroke are not clearly defined. We performed a genetic association study to assess the association of 56 previously characterized gene variants in 34 candidate genes from cardiovascular disease related biological pathways with ischemic stroke and cerebral hemorrhage in a Chinese population.Methods
There were 1280 stroke patients (1101 with ischemic stroke and 179 with cerebral hemorrhage) and 1380 controls in the study. The genotypes for 56 polymorphisms of 34 candidate genes were determined by the immobilized probe approach and the associations of gene polymorphisms with ischemic stroke and cerebral hemorrhage were performed by logistic regression under an allelic model.Results
After adjusting for age, sex, BMI and hypertension status by logistic regression analysis, we found that NPPA rs5063 was significantly associated with both ischemic stroke (odds ratio [OR] 0.69; 95% confidence interval [CI], 0.52 to 0.90; P = 0.006) and cerebral hemorrhage(OR = 0.39; 95%CI, 0.19 to 0.78; P = 0.007). In addition, MTHFR rs1801133 also was associated with cerebral hemorrhage (OR = 1.48; 95%CI, 1.16 to1.89; P = 0.001) but not with ischemic stroke (OR = 1.08; 95%CI, 0.96 to1.22; P = 0.210). After false discovery rate (FDR) correction, the association of NPPA rs5063 and MTHFR rs1801133 with cerebral hemorrhage remained significant.Conclusions
The NPPA rs5063 is associated with reduced risk for cerebral hemorrhage and MTHFR rs1801133 is associated with increased risk of cerebral hemorrhage in a Chinese population. 相似文献14.
Miaofei Xu Yufeng Qin Jianhua Qu Chuncheng Lu Ying Wang Wei Wu Ling Song Shoulin Wang Feng Chen Hongbing Shen Jiahao Sha Zhibin Hu Yankai Xia Xinru Wang 《PloS one》2013,8(11)
Background
Oligozoospermia is one of the severe forms of idiopathic male infertility. However, its pathology is largely unknown, and few genetic factors have been defined. Our previous genome-wide association study (GWAS) has identified four risk loci for non-obstructive azoospermia (NOA).Objective
To investigate the potentially functional genetic variants (including not only common variants, but also less-common and rare variants) of these loci on spermatogenic impairment, especially oligozoospermia.Design, Setting, and Participants
A total of 784 individuals with oligozoospermia and 592 healthy controls were recruited to this study from March 2004 and January 2011.Measurements
We conducted a two-stage study to explore the association between oligozoospermia and new makers near NOA risk loci. In the first stage, we used next generation sequencing (NGS) in 96 oligozoospermia cases and 96 healthy controls to screen oligozoospermia-susceptible genetic variants. Next, we validated these variants in a large cohort containing 688 cases and 496 controls by SNPscan for high-throughput Single Nucleotide Polymorphism (SNP) genotyping.Results and Limitations
Totally, we observed seven oligozoospermia associated variants (rs3791185 and rs2232015 in PRMT6, rs146039840 and rs11046992 in Sox5, rs1129332 in PEX10, rs3197744 in SIRPA, rs1048055 in SIRPG) in the first stage. In the validation stage, rs3197744 in SIRPA and rs11046992 in Sox5 were associated with increased risk of oligozoospermia with an odds ratio (OR) of 4.62 (P = 0.005, 95%CI 1.58-13.4) and 1.82 (P = 0.005, 95%CI 1.01-1.64), respectively. Further investigation in larger populations and functional characterizations are needed to validate our findings.Conclusions
Our study provides evidence of independent oligozoospermia risk alleles driven by variants in the potentially functional regions of genes discovered by GWAS. Our findings suggest that integrating sequence data with large-scale genotyping will serve as an effective strategy for discovering risk alleles in the future. 相似文献15.
Adriana Huertas-Vazquez Christopher P. Nelson Xiuqing Guo Kyndaron Reinier Audrey Uy-Evanado Carmen Teodorescu Jo Ayala Katherine Jerger Harpriya Chugh WTCCC+ Peter S. Braund Panos Deloukas Alistair S. Hall Anthony J. Balmforth Michelle Jones Kent D. Taylor Sara L. Pulit Christopher Newton-Cheh Karen Gunson Jonathan Jui Jerome I. Rotter Christine M. Albert Nilesh J. Samani Sumeet S. Chugh 《PloS one》2013,8(4)
Background
Recent genome-wide association studies (GWAS) have identified novel loci associated with sudden cardiac death (SCD). Despite this progress, identified DNA variants account for a relatively small portion of overall SCD risk, suggesting that additional loci contributing to SCD susceptibility await discovery. The objective of this study was to identify novel DNA variation associated with SCD in the context of coronary artery disease (CAD).Methods and Findings
Using the MetaboChip custom array we conducted a case-control association analysis of 119,117 SNPs in 948 SCD cases (with underlying CAD) from the Oregon Sudden Unexpected Death Study (Oregon-SUDS) and 3,050 controls with CAD from the Wellcome Trust Case-Control Consortium (WTCCC). Two newly identified loci were significantly associated with increased risk of SCD after correction for multiple comparisons at: rs6730157 in the RAB3GAP1 gene on chromosome 2 (P = 4.93×10−12, OR = 1.60) and rs2077316 in the ZNF365 gene on chromosome 10 (P = 3.64×10−8, OR = 2.41).Conclusions
Our findings suggest that RAB3GAP1 and ZNF365 are relevant candidate genes for SCD and will contribute to the mechanistic understanding of SCD susceptibility. 相似文献16.
Edna J. L. Barbosa Camilla A. M. Glad Anna G. Nilsson Niklas Bosaeus Helena Filipsson Nystr?m Per-Arne Svensson Bengt-?ke Bengtsson Staffan Nilsson Ingvar Bosaeus Cesar Luiz Boguszewski Gudmundur Johannsson 《PloS one》2014,9(8)
Objectives
Growth hormone deficiency (GHD) in adults is associated with decreased extracellular water volume (ECW). In response to GH replacement therapy (GHRT), ECW increases and blood pressure (BP) reduces or remains unchanged. Our primary aim was to study the association between polymorphisms in genes related to renal tubular function with ECW and BP before and 1 year after GHRT. The ECW measures using bioimpedance analysis (BIA) and bioimpedance spectroscopy (BIS) were validated against a reference method, the sodium bromide dilution method (Br−).Design and Methods
Using a candidate gene approach, fifteen single-nucleotide polymorphisms (SNPs) in nine genes with known impact on renal tubular function (AGT, SCNN1A, SCNN1G, SLC12A1, SLC12A3, KCNJ1, STK39, WNK1 and CASR) were genotyped and analyzed for associations with ECW and BP at baseline and with their changes after 1 year of GHRT in 311 adult GHD patients. ECW was measured with the Br−, BIA, and BIS.Results
Both BIA and BIS measurements demonstrated similar ECW results as the reference method. At baseline, after adjustment for sex and BMI, SNP rs2291340 in the SLC12A1 gene was associated with ECW volume in GHD patients (p = 0.039). None of the SNPs influenced the ECW response to GHRT. One SNP in the SLC12A3 gene (rs11643718; p = 0.024) and three SNPs in the SCNN1G gene [rs5723 (p = 0.02), rs5729 (p = 0.016) and rs13331086 (p = 0.035)] were associated with the inter-individual differences in BP levels at baseline. A polymorphism in the calcium-sensing receptor (CASR) gene (rs1965357) was associated with changes in systolic BP after GHRT (p = 0.036). None of these associations remained statistically significant when corrected for multiple testing.Conclusion
The BIA and BIS are as accurate as Br− to measure ECW in GHD adults before and during GHRT. Our study provides the first evidence that individual polymorphisms may have clinically relevant effects on ECW and BP in GHD adults. 相似文献17.
Mark Bi Wen Hong Linda Kao Eric Boerwinkle Ron C. Hoogeveen Laura J. Rasmussen-Torvik Brad C. Astor Kari E. North Josef Coresh Anna K?ttgen 《PloS one》2010,5(7)
Objective
The minor T-allele of rs780094 in the glucokinase regulator gene (GCKR) associates with a number of metabolic traits including higher triglyceride levels and improved glycemic regulation in study populations of mostly European ancestry. Using data from the Atherosclerosis Risk in Communities (ARIC) Study, we sought to replicate these findings, examine them in a large population-based sample of African American study participants, and to investigate independent associations with other metabolic traits in order to determine if variation in GKCR contributes to their observed clustering. In addition, we examined the association of rs780094 with incident diabetes, coronary heart disease (CHD), and stroke over up mean follow-up times of 8, 15, and 15 years, respectively.Research Design and Methods
Race-stratified analyses were conducted among 10,929 white and 3,960 black participants aged 45–64 at baseline assuming an additive genetic model and using linear and logistic regression and Cox proportional hazards models.Results
Previous findings replicated among white participants in multivariable adjusted models: the T-allele of rs780094 was associated with lower fasting glucose (p = 10−7) and insulin levels (p = 10−6), lower insulin resistance (HOMA-IR, p = 10−9), less prevalent diabetes (p = 10−6), and higher CRP (p = 10−8), 2-h postprandial glucose (OGTT, p = 10−6), and triglyceride levels (p = 10−31). Moreover, the T-allele was independently associated with higher HDL cholesterol levels (p = 0.022), metabolic syndrome prevalence (p = 0.043), and lower beta-cell function measured as HOMA-B (p = 0.011). Among black participants, the T-allele was associated only with higher triglyceride levels (p = 0.004) and lower insulin levels (p = 0.002) and HOMA-IR (p = 0.013). Prospectively, the T-allele was associated with reduced incidence of diabetes (p = 10−4) among white participants, but not with incidence of CHD or stroke.Conclusions
Our findings indicate rs780094 has independent associations with multiple metabolic traits as well as incident diabetes, but not incident CHD or stroke. The magnitude of association between the SNP and most traits was of lower magnitude among African American compared to white participants. 相似文献18.
Lawrence C. M. Lau Li Ma Alvin L. Young Shi Song Rong Vishal Jhanji Marten E. Brelen Chi Pui Pang Li Jia Chen 《PloS one》2014,9(10)
Topic
A meta-analysis of TCF4 and PTPRG gene variants in Fuchs'' corneal dystrophy (FCD).Clinical relevance
To identify novel genetic markers in patients with FCD in different ethnic populations.Methods
MEDLINE and EMBASE were searched for eligible genetic studies on TCF4 and PTPRG in FCD. Odds ratios (OR) and 95% confidence intervals (CI) of each single-nucleotide polymorphism (SNP) in allelic, dominant and recessive models were estimated using fixed-effect model if I2<50% in the test for heterogeneity, otherwise the random effects model was used.Results
Thirty-three records were obtained, with 8 being suitable for meta-analysis, which included five SNPs in TCF4 and two in PTPRG. There were 1610 FCD patients and 1565 controls tested for TCF4 rs613872. This SNP was strongly associated with FCD in Caucasians (P = 5.0×10−106), with the risk allele G conferring an OR of 3.95 (95% CI: 3.49–4.46). A further 4 TCF4 SNPs (rs17595731, rs2286812, rs618869 and rs9954153) were also significantly associated with FCD in Caucasians (P<10−8). However, we found no SNP associated with FCD in Chinese. In addition, there was no significant association between FCD and PTPRG.Conclusion
TCF4 rs613872 is strongly associated with FCD in Caucasians but not in Chinese, which may suggest ethnic diversity in FCD SNP associations. SNPs in PTPRG were not associated with FCD in Caucasians or Chinese populations. Results of this meta-analysis indicate the need for larger-scale and multi-ethnic genetic studies on FCD to further explore the associated gene variants and their roles on the mechanism and genetic basis of FCD. 相似文献19.
Lingjun Zhu Mulong Du Dongying Gu Lan Ma Haiyan Chu Na Tong Jinfei Chen Zhengdong Zhang Meilin Wang 《PloS one》2013,8(3)
Background
A recent genome-wide association study has identified a new genetic variant rs7758229 in SLC22A3 for colorectal cancer susceptibility in a Japanese population, but it is unknown whether this newly identified variant is associated with colorectal cancer in other populations, including the Chinese population.Methods
We examined the associations between rs7758229 and colorectal cancer risk among 1,147 cases and 1,203 controls matched by age and sex. Logistic regression model was used to assess the associations.Results
No significant association was found between rs7758229 and colorectal cancer risk (OR = 0.95, 95%CI = 0.84–1.09, P = 0.463). Similar results were observed in the stratification of tumor location (OR = 0.94, 95%CI = 0.80–1.11, P = 0.481 for colon cancer, and OR = 0.96, 95%CI = 0.82–1.13, P = 0.621 for rectum cancer).Conclusions
Our findings did not support an association between rs7758229 in 6q26-q27 and the risk of colorectal cancer in a Chinese population. 相似文献20.
Li J Yang D He Y Wang M Wen Z Liu L Yao J Matsuda K Nakamura Y Yu J Jiang X Sun S Liu Q Jiang X Song Q Chen M Yang H Tang F Hu X Wang J Chang Y He X Chen Y Lin J 《PloS one》2011,6(8):e24221