title: Common variants in or near FGF5, CYP17A1 and MTHFR genes are associated with blood pressure and hypertension in Chinese Hans.
abstract: OBJECTIVE
  Recent genome-wide association studies have identified a number of variants influencing blood pressure. We aimed to examine whether these associations can be replicated in Chinese.
  
  
  METHODS
  We genotyped eight of these variants (in or near FGF5, CYP17A1, MTHFR, ZNF652, PLCD3, ATP2B1, c10orf107) in a population-based cohort of Chinese Hans (N = 3210). Logistics regression and generalized linear analyses were applied to test for association of each variant with hypertension risk and blood pressure (BP), BMI, waistline and high-sensitivity C-reactive protein (hsCRP), respectively.
  
  
  RESULTS
  Six variants showed directionally consistent association with blood pressure and risk of hypertension, of which four (FGF5, two in CYP17A1, MTHFR) reached significance. The associations were most pronounced for FGF5-rs16998073 [SBP: β = 1.97 mmHg/allele, P = 0.0006; DBP: β = 0.95 mmHg/allele, P = 0.0008, hypertension: odds ratio (OR) 1.36/allele, P = 0.0001]. Effect size of FGF5-rs16998073 on SBP and hypertension were significantly more pronounced in Han Chinese compared to white Europeans. None of these variants was associated with BMI, waistline or hsCRP that are the well established risk factors for hypertension. The genetic risk score, calculated as the sum of BP-increasing alleles of FGF5-rs16998073, CYP17A1-rs11191548, CYP17A1-rs1004467 and MTHFR-rs17367504, was significantly associated with increased SBP (1.16 mmHg/allele, P = 9.01E-5), DBP (0.51 mmHg/allele, P = 4.40E-4) and hypertension risk (OR = 1.22/allele, P = 2.74E-7).
  
  
  CONCLUSIONS
  Variants in or near FGF5, CYP17A1 and MTHFR contributed to variation in BP and hypertension risk. Effect sizes of these three loci tended to be larger in Chinese than in white Europeans, but more studies with larger sample size are required for a definitive conclusion.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Huaixing
authors.initials: H
authors.lastname: Li
authors.forename: Qibin
authors.initials: Q
authors.lastname: Qi
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Gan
authors.forename: Ruth Jf
authors.initials: RJ
authors.lastname: Loos
authors.forename: Xu
authors.initials: X
authors.lastname: Lin
mesh_terms: D001794:Blood Pressure / Q000235:genetics*; D002681:China; D005006:Ethnicity; D005260:Female; D051521:Fibroblast Growth Factor 5 / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: C496449:FGF5 protein, human; D051521:Fibroblast Growth Factor 5; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D042965:Methylenetetrahydrofolate Reductase (NADPH2)