title: Genetic variations in CYP17A1, CACNB2 and PLEKHA7 are associated with blood pressure and/or hypertension in She ethnic minority of China.
abstract: OBJECTIVE
  Two large-scale genome-wide association studies (GWAs) have identified multiple variants associated with blood pressure (BP) or hypertension. The present study was to investigate whether some variations were associated with BP traits and hypertension or even prehypertension in adult She ethnic minority of China.
  
  
  METHODS
  The population of the present study comprised 4460 (1979 males and 2481 females, respectively) unrelated she ethnic minority based on a cross-sectional study from Ningde City in Fujian province of China. There were 1692 hypertensives, 1600 prehypertensives and 1168 normotensive controls, respectively. We genotyped 7 variants in CYP17A1, PLEKHA7, CACNB2, ATP2B1, TBX3-TBX5, CSK-ULK3 and SH2B3 reported by the previous GWAs on Europeans. All analyses were performed in an additive genetic model.
  
  
  RESULTS
  As the minor allele of rs653178 in/near SH2B3 was very rare with the frequency of 0.018, we excluded this single nucleotide polymorphism (SNP) in the further analyses. Of the other 6 loci, linear regression analyses revealed that rs11191548 in CYP17A1 and rs11014166 in CACNB2 were significantly associated with systolic BP (β = -1.17, P = 0.002 and β = -0.50, P = 0.006, respectively), while only SNP rs11191548 was significantly associated with diastolic BP (β = -0.56, P=0.002) after adjusted by age, sex and BMI. Two variants in CACNB2 and PLEKHA7 were found to be significantly related to hypertension (odds ratios [OR] and (95% confidence interval [CI]): 0.79 (0.65-0.97) and 1.19 (1.01-1.41), respectively) in logistic regression analyses after adjusted by age, sex and BMI. In addition, we found that combined risk alleles of the 6 SNPs increased risk of hypertension in a stepwise fashion (P for trend < 0.001). However, none of the 6 SNPs was significantly associated with BMI or prehypertension status. While logistic analysis showed that subjects with cumulative risk alleles more than 9 had significantly higher risk for prehypertension (adjusted OR: 3.10, P < 0.001) compared with those with risk alleles less than 4.
  
  
  CONCLUSIONS
  We replicated that variations in CYP17A1, CACNB2 and PLEKHA7 were related to BP traits and/or hypertension in She population. In addition, although we failed to observe single gene associated with prehypertension, we first found that conjoint effect of multiple risk alleles on BP might increase the risk of progressing to prehypertension.
authors.affiliation: Department of Endocrinology, Ningde Municipal Hospital, Ningde 352100, China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Lin
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Lai
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Baoying
authors.initials: B
authors.lastname: Huang
authors.forename: Zichun
authors.initials: Z
authors.lastname: Chen
authors.forename: Shaoheng
authors.initials: S
authors.lastname: Zhu
authors.forename: Jin
authors.initials: J
authors.lastname: Yao
authors.forename: Qiqin
authors.initials: Q
authors.lastname: Jiang
authors.forename: Huibin
authors.initials: H
authors.lastname: Huang
authors.forename: Junping
authors.initials: J
authors.lastname: Wen
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008913:Minority Groups; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D058246:Prehypertension / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: C107597:CACNB2 protein, human; D020746:Calcium Channels, L-Type; D002352:Carrier Proteins; C533786:PLEKHA7 protein, human; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase