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. DESIGN AND 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.
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. DESIGN AND 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.