title: Association study of common variations of FBN1 gene and essential hypertension in Han Chinese population.
abstract: Fibrillin-1 (FBN1) was reported to have impact on the physiological arterial stiffness and vascular remodeling with hypertension of recent years. In the previous study we reported the association of four functional single nucleotide polymorphisms (SNPs) of FBN1 gene and hypertension. Here, we further investigate the association of four tagging SNPs (tagSNPs) which covered remain genetic variation blocks of FBN1 gene with hypertension, blood pressure and efficacy of antihypertensive in a South Han Chinese population. A case-control study including 2,012 hypertension cases and 2,116 controls age- and sex-matched controls was conducted from a community-based population and four candidate tagSNPs of the FBN1 gene were genotyped. Association analysis by multiple logistic regression was conducted for allele, genotype and haplotype and hypertension, blood pressure trait and control status with antihypertensive. General linear model was applied to compare blood pressure levels between genotypes. The association of rs17361868 and hypertension was statistically significant and that was further observed in female, ≥55 years, non-smoking and non-drinking populations (P < 0.05). Significant association of rs668842, rs11635140 and hypertension were observed in <55 years population as well as the later in female and non-smoking populations respectively. Haplotype G-T constructed of rs668842 and rs11635140 was significantly associated with hypertension comparing to reference haplotype A-C (P = 0.022). Normally distributed square root of TGF-β1 (pg/ml) of hypertension cases (148.56 ± 66.46) was significantly higher than that of control (128.52 ± 65.11), P = 0.008. Furthermore, TGF-β1 was significantly correlated with SBP (r = 0.135, P = 0.018) and DBP (r = 0.154, P = 0.007) respectively whereas no statistical difference of blood pressure or TGF-β1 was observed between genotypes. Remarkably, rs17361868 were significantly associated with the status of blood pressure in the patients taking three of the antihypertensive drugs, Zhen Ju Jiang Ya tablets, Jiang Ya tablet and compound reserpine (P < 0.05). The present study provides further association evidence of FBN1 gene polymorphisms and hypertension, antihypertensive efficacy. Further replication of these results via association or prospective studies conducted in other populations is warranted.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Chen
authors.forename: Song
authors.initials: S
authors.lastname: Yang
authors.forename: Xianghai
authors.initials: X
authors.lastname: Zhao
authors.forename: Jiahui
authors.initials: J
authors.lastname: Shen
authors.forename: Hairu
authors.initials: H
authors.lastname: Wang
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Chen
authors.forename: Yanni
authors.initials: Y
authors.lastname: Ji
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Xuecai
authors.initials: X
authors.lastname: Wang
authors.forename: Junming
authors.initials: J
authors.lastname: Tang
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Lu
authors.forename: Shufeng
authors.initials: S
authors.lastname: Chen
authors.forename: Laiyuan
authors.initials: L
authors.lastname: Wang
authors.forename: Hongfan
authors.initials: H
authors.lastname: Li
authors.forename: Chong
authors.initials: C
authors.lastname: Shen
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D000075222:Essential Hypertension; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D053773:Transforming Growth Factor beta1 / Q000097:blood; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D053773:Transforming Growth Factor beta1; C000605722:FBN1 protein, human; D054392:Adipokines