title: CYP11B2 gene polymorphisms and hypertension in highlanders accustomed to high salt intake.
abstract: BACKGROUND
  High salt intake is the main determinant of hypertension. The alleles, which once had adaptive value in the salt-poor environment, by promoting salt retention, now induce hypertension. It would be interesting to determine whether the variant alleles of the aldosterone synthase gene (CYP11B2), if related to exaggerated expression/altered activity, are associated with hypertension when combined with a salt-rich diet.
  
  
  OBJECTIVE
  To investigate the -344T/C, K173R and intron-2 conversion polymorphisms of CYP11B2 for an association with hypertension in highlanders accustomed to a high salt intake.
  
  
  METHODS
  Three CYP11B2 polymorphisms were compared with respect to frequencies and clinical characteristics in 190 normotensive highlanders (NHLs) and 100 hypertensive highlanders (HHLs). One-way ANOVA, chi2 test and logistic regression analysis were carried out to investigate the association of these polymorphisms with hypertension.
  
  
  RESULTS
  The HHLs had significantly higher systolic blood pressure (SBP), diastolic blood pressure (DBP) (P < 0.0001), body mass index (BMI) (P = 0.0002), plasma aldosterone levels (P = 0.03) and aldosterone to plasma renin ratio (ARR) (P < 0.0001) and lower plasma renin activity (PRA) (P = 0.007). The -344T/C and K173R polymorphisms were in complete linkage disequilibrium with each other and the intron-2 conversion allele was in absolute association with the T allele. The TC/CC genotypes correlated with higher BMI when compared with TT genotype in the NHLs and the HHLs (P = 0.002 and 0.004, respectively). The intron-2 conversion heterozygotes/homozygotes correlated with higher SBP in the HHLs (P = 0.03) and significantly higher ARR when compared to IwIw (P = 0.02). Genotype combinations between the -344T/C and intron-2 conversion polymorphisms revealed that combinations with TC or CC genotypes inclined towards higher BMI in both the groups (P < 0.05).
  
  
  CONCLUSIONS
  Our findings showed a correlation of C allele with high BMI, suggesting that -344T/C polymorphism is in linkage disequilibrium with a functional polymorphism on the adjacent 11-beta hydroxylase gene. The correlation of the intron-2 conversion allele with high SBP and ARR associates it with hypertension. The intron-2 conversion could be a functional variant, since it has been suggested to lead to overexpression of the gene; however, the presence of another functional variant in linkage disequilibrium within the gene cannot be ruled out.
authors.affiliation: Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Charu
authors.initials: C
authors.lastname: Rajput
authors.forename: Kalpana
authors.initials: K
authors.lastname: Makhijani
authors.forename: Tsering
authors.initials: T
authors.lastname: Norboo
authors.forename: Farhat
authors.initials: F
authors.lastname: Afrin
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Sharma
authors.forename: S Tazeen
authors.initials: ST
authors.lastname: Pasha
authors.forename: M A Qadar
authors.initials: MA
authors.lastname: Pasha
mesh_terms: D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D015992:Body Mass Index; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D004777:Environment; D005247:Feeding Behavior; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000178:diet therapy / Q000235:genetics*; D007438:Introns; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012083:Renin / Q000097:blood; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*
chemical_list: D017673:Sodium Chloride, Dietary; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D012083:Renin