Abstract

ABSTRACT Background: The consanguineous marriages are very common worldwide with a risk of acquiring a recessive gene mainly in multi- generational tradition of first cousin marriages. In Pakistan, the Muslim majority has more prevalence of practicing consanguinity than the Hindus. Aims &
Objective: We studied the Serene Threonine Kinase-39 Single Nucleotide A > G Polymorphism rs35929607; and comparatively analyzed recessive versus dominant mode of transmission of essential hypertension by plotting genotypes on the pedigree maps of both indicated populations.
Materials and Methods: This was Cross sectional, case-controlled and pedigree based study. After getting an approval from the Aga Khan University Ethical Review Committee, we recruited N=130 members from 4 pedigrees (n=67 from 2 consanguineous pedigrees: 25 males and 42 females; and n=63 from 2 non-consanguineous pedigrees with 32 males and 31 females). We genotyped N=96 participants and calculated the prevalence of genotypes and frequencies of the allele A and G. Prevalence of AA, GG and AG genotypes were calculated. Assessment for concordance with HWE was performed. Chi-square and odds ratio with 95% confidence limitation for frequencies of allele A and allele G was calculated. Relation of EHTN transmission with the homozygosity and heterozygosity was plotted against the participants in the pedigree trees.
Results: Consanguineous pedigrees showed frequencies of 62.26% for AG, 35.85% for AA and 1.89% for GG genotypes; and 2 frequency of reference allele (A) was 67.0% and of rare allele (G) 33.0% (χ = 8.80 and p-value 0.003). Non-consanguineous pedigrees showed 53.49% for AG, 44.19% for AA and 2.33% for GG and frequency of reference allele (A) 71.0% and rare allele (G) 2 was 29.0% (χ = 3.79 and p-value 0.0514). The p-values indicate that both populations are not falling in concordance with Hardy Weinberg Equilibrium (HWE) and are stratified. Conclusion: Consanguineous pedigrees in context to STK-39 SNP rs35929607, showed recessive pattern of inheritance as opposed to the non-consanguineous cohort showing dominant pattern of inheritance of essential hypertension. This outcome needs further confirmation by carrying out study at a broader scale by recruiting large sample size.