title: Genetic Variation in the Human SORBS1 Gene is Associated With Blood Pressure Regulation and Age at Onset of Hypertension: A SAPPHIRe Cohort Study.
abstract: 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.
authors.affiliation: From the Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (T-JC, Y-CC, L-MC); The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan (W-CW); Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan (W-CW, C-AH); Department of Endocrinology and Metabolism, Tri-Service General Hospital, Taipei, Taiwan (C-TH); Institute of Public Health, National Yang-Ming University, Taipei, Taiwan (M-WL); Department of Medical Research & Education, Taipei Veterans General Hospital, Taipei, Taiwan (M-WL); Department of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung, Taiwan (WH-HS); Graduate Institute of Medical Genomics and Proteomics, National Taiwan University Medical College, Taipei, Taiwan (Y-CC); Division of Cardiovascular Medicine, Falk CVRC, Stanford University School of Medicine, Stanford, CA (TQ); Los Angles Biomedical Research Institute, Los Angeles, CA (IC, JR); Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan (L-MC).
authors.forename: Tien-Jyun
authors.initials: TJ
authors.lastname: Chang
authors.forename: Wen-Chang
authors.initials: WC
authors.lastname: Wang
authors.forename: Chao A
authors.initials: CA
authors.lastname: Hsiung
authors.forename: Chih-Tsueng
authors.initials: CT
authors.lastname: He
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Wayne Huey-Herng
authors.initials: WH
authors.lastname: Sheu
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chang
authors.forename: Tom
authors.initials: T
authors.lastname: Quertermous
authors.forename: Ida
authors.initials: I
authors.lastname: Chen
authors.forename: Jerome
authors.initials: J
authors.lastname: Rotter
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
mesh_terms: D000328:Adult; D017668:Age of Onset; D001794:Blood Pressure / Q000235:genetics; D015331:Cohort Studies; D003971:Diastole; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D013599:Systole; D013624:Taiwan / Q000453:epidemiology
chemical_list: D008840:Microfilament Proteins; C432967:SORBS1 protein, human