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Genetic variation of SORBS1 gene is associated with glucose homeostasis and age at onset of diabetes: A SAPPHIRe Cohort Study.

ABSTRACT: The SORBS1 gene plays an important role in insulin signaling. We aimed to examine whether common single-nucleotide polymorphisms (SNPs) of SORBS1 are associated with prevalence and incidence of diabetes, age at onset of diabetes, and the related traits of glucose homeostasis. A total of 1135 siblings from 492 ethnic Chinese families were recruited at baseline, and 630 were followed up for 5.19?±?0.96 years. Nine SNPs including rs7081076, rs2281939, rs3818540, rs2274490, rs61739184, rs726176, rs2296966, rs17849148, and rs3193970 were genotyped and examined. To deal with correlated data of subjects within the same families, the generalized estimating equations approach was applied throughout all association analyses. The GG genotype of rs2281939 was associated with a higher risk of diabetes at baseline, an earlier onset of diabetes, and higher steady-state plasma glucose levels in the modified insulin suppression test. The minor allele T of rs2296966 was associated with higher prevalence and incidence of diabetes, an earlier onset of diabetes, and higher 2-h glucose during oral glucose tolerance test. These two SNPs revealed independent associations with age of diabetes onset as well as risk of diabetes at baseline. These findings supported that SORBS1 gene participates in the pathogenesis of diabetes.

SUBMITTER: Chang TJ

PROVIDER: S-EPMC6043583 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Genetic variation of SORBS1 gene is associated with glucose homeostasis and age at onset of diabetes: A SAPPHIRe Cohort Study.

Chang Tien-Jyun TJ Wang Wen-Chang WC Hsiung Chao A CA He Chih-Tsueng CT Lin Ming-Wei MW Sheu Wayne Huey-Herng WH Chang Yi-Cheng YC Quertermous Tom T Chen Yii-Der Ida YI Rotter Jerome I JI Chuang Lee-Ming LM

Scientific reports 20180712 1

The SORBS1 gene plays an important role in insulin signaling. We aimed to examine whether common single-nucleotide polymorphisms (SNPs) of SORBS1 are associated with prevalence and incidence of diabetes, age at onset of diabetes, and the related traits of glucose homeostasis. A total of 1135 siblings from 492 ethnic Chinese families were recruited at baseline, and 630 were followed up for 5.19 ± 0.96 years. Nine SNPs including rs7081076, rs2281939, rs3818540, rs2274490, rs61739184, rs726176, rs2 ...[more]

PMID: 30002559

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Project description:Essential hypertension is a complex disease involving multiple genetic and environmental factors. A human gene containing a sorbin homology domain and 3 SH3 domains in the C-terminal region, termed SORBS1, plays a significant role in insulin signaling. We previously found a significant association between the T228A polymorphism and insulin resistance, obesity, and type 2 diabetes. It has been hypothesized that a set of genes responsible for insulin resistance may be closely linked with genes susceptible to the development of hypertension. Identification of insulin resistance-related genetic factors may, therefore, enhance our understanding of essential hypertension. This study aimed to examine whether common SORBS1 genetic variations are associated with blood pressure and age at onset of hypertension in an ethnic Chinese cohort.We genotyped 9 common tagged single nucleotide polymorphisms of the SORBS1 gene in 1136 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study. Blood pressure was measured upon enrolment. The associations of the SORBS1 single nucleotide polymorphisms with blood pressure and the presence of hypertension were analyzed with a generalized estimating equation model. We used the false-discovery rate measure Q value with a cutoff <0.1 to adjust for multiple comparisons. In the Cox regression analysis for hypertension-free survival, a robust sandwich variance estimator was used to deal with the within-family correlations with age at onset of hypertension. Gender, body mass index, and antihypertension medication were adjustment covariates in the Cox regression analysis.In this study, genetic variants of rs2281939 and rs2274490 were significantly associated with both systolic and diastolic blood pressure. A genetic variant of rs2274490 was also significantly associated with the presence of hypertension. Furthermore, genetic variants of rs2281939 and rs2274490 were associated with age at onset of hypertension after adjustment for gender, body mass index, and antihypertension medication.In conclusion, we provide evidence for an association between common SORBS1 genetic variations and blood pressure, presence of hypertension, and age at onset of hypertension. The biological mechanism of genetic variation associated with blood pressure regulation needs further investigation.

Dataset Information

Genetic variation of SORBS1 gene is associated with glucose homeostasis and age at onset of diabetes: A SAPPHIRe Cohort Study.

Publications

Genetic variation of SORBS1 gene is associated with glucose homeostasis and age at onset of diabetes: A SAPPHIRe Cohort Study.

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