Significance of AGT haplotypes and genotypes-combinations versus single nucleotide polymorphisms in hyprtension: togetherness does matter

سال انتشار: 1397
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 551

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شناسه ملی سند علمی:

JR_PMJ-3-9_011

تاریخ نمایه سازی: 23 آبان 1397

چکیده مقاله:

Renin-angiotensin system gene polymorphisms are associated with essential hypertension; angiotensinogen (AGT) gene variants are considered potential genetic risk factors. The aim of this study was to investigate the contribution of the G-6A, T174M, M235T polymorphisms, respective genotypic interactions and haplotypes towards essential hypertension. Methods In a case-control design, 810 consecutive ethnically-matched unrelated subjects comprising 450 hypertensives and 360 controls were recruited. Genotyping by PCR-RFLP, genotypes-combination and haplotype analyses were performed. Results The G-6A and M235T polymorphisms differed significantly (P = 0,007, OR=1.9,95% CI =1.2-2.9; P<0.0001, OR =3.7.95% CI =2.3-5.7, respectively), wherein the-6A and 235T mutant alleles were over-represented in hypertensives (P < 0.0001, cach). The genotypes combinations of the three polymorphisms having 6 wild-type alleles versus the remaining resulted in odds ratio of 2.4 (P < 0.0001), further as the number of mutant alleles in a combination increased, the systolic, diastolic and mean blood pressure increased. The overall likelihood of haplotypes profile difference between the two groups was highly significant (P < 0.0001). Overrepresentation of the haplotypes viz., A/1741, 174T/235T, A/235T, A/174T/235T in hypertensives, and G/174T, 174T/235M, G/235M, G/174T/235M in controls, was identified as risk and protective haplotypes (P<0.0001. each). respectively. Conclusion The-6A and 235T alleles and respective homozygous genotypes were independently associated with hypertension susceptibility. The interaction of 174T-allele with M235T and G-6A polymorphisms in combinations or haplotypes emerged significant. The 3-locus haplotypes were distinct by the prevalence of 235T-allele in hypertensives and 235M-allele in controls.

نویسندگان

azim nejatizadeh

Institute of Genomics and Integrative Biology, Delhi, India, Department of Biochemistry, Hamdard University, New Delhi, India

rahul kumar

Institute of Genomics and Integrative Biology, Delhi, India

tserng stobdan

Institute of Genomics and Integrative Biology, Delhi, India

ak goel

hindu rao hospital deptt of medicine delhi,india