eNOS Glu298Asp (rs1799983) and AGT Met235Thr (rs699) polymorphisms in adverse cardiometabolic phenotypes: A study among Bhil tribal population of India

Background: Cardiometabolic adversities constitute an enormous public health challenge. Along with lifestyle/ socio-cultural determinants, disease outcome is modulated by genetic variants as well. Genetic polymorphisms like eNOS Glu298Asp (rs1799983) and AGT Met235Thr (rs699) have been identified as significant contributors to cardiometabolic phenotypes (obesity, hypertension and dyslipidemia) due to their role in vascular homeostasis, endothelial function, cardiac performance, etc. However, the association of these two genetic polymorphisms with cardiometabolic phenotypes among Indian Bhil tribal population have not yet been determined.Methods: This was a cross-sectional study conducted among Bhil tribal population from India. The study recruited 297 participants aged 25-75 years through door-to-door household survey. Data on demographic and lifestyle variables were collected using a pre-tested modified interview schedule. Anthropometric (height, weight, waist circumference and hip circumference) and physiological (systolic and diastolic blood pressure) parameters were measured to define obesity and hypertension. Fasting blood samples were collected and serum was separated for lipid profiling (TC, TG, HDL-C, LDL-C and VLDL-C) and DNA was extracted from whole blood for genetic analysis (PCR-RFLP). Multivariable logistic regression was employed to identify association of genetic polymorphisms with cardiometabolic phenotypes.Results: The frequency of GG, GT and TT genotypes of eNOS rs1799983 were 52.86%, 45.45% and 1.68%, respectively and 0.24 minor allele frequency (MAF). The frequency of TT, TC and CC genotypes of AGT rs699 were 37.71%, 41.41% and 20.88%, respectively and 0.42 MAF. GT genotype and T allele (GT + TT genotypes) of rs1799983 were inversely associated with high WC, prehypertension, low HDL-C, and high LDL-C (all adjusted OR values <1 and p < 0.05). Conversely, TC and C allele (TC + CC genotypes) of rs699 were significantly associated with dyslipidemia, specifically high TC, TG and VLDL-C (all adjusted OR values >1.6 and p < 0.05). Also, individuals with the combination of high TC and TC genotype or C allele of rs699 appeared to have survival disadvantage at older age.Conclusion: With high frequency of AGT rs699 mutant C allele and significant association with dyslipidemia, our study suggests screening of candidate gene polymorphisms for cardiometabolic diseases among tribal populations to identify risk genotypes or alleles, which may pave way for future pharmacogenetic therapy and precision medicine.