Association analyses of NsiI RFLP of human insulin receptor gene in hypertensives

Abstract

Plasma angiotensinogen is elevated in essential hypertensives and shows a strong correlation with blood pressure. Patients with hypertension often display insulin resistance and we have found previously an association of a Rsal RFLP in intron 9 of the insulin receptor gene (INSR) with hypertension. Since insulin resistance is accompanied by hyperinsulinaemia and insulin can stimulate angiotensinogen production, we hypothesized that hypertension‐associated genotypes of INSR may be associated with elevation in plasma angiotensinogen. We used PCR to detect a Nsil RFLP in exon 8 of INSR and examined its relationship with plasma angiotensinogen, as well as hypertension, in 134 Caucasian hypertensives with two hypertensive parents and in 126 normotensives. Plasma angiotensinogen tracked weakly with the major allele of the Nsil RFLP in hypertensives (p=0.08). Moreover, the frequency of this allele was higher in lean hypertensives than in lean normotensives (p<0.05) and in normolipidaemic hypertensives than normolipidaemic normotensives (p<0.02). The present study thus suggests that there could be a relationship of plasma angiotensinogen with INSR genotype, and of each with hypertension.

ScreeningCodon 233, 234 and 276 Polymorphisms in Exon 3 ofInsulin Receptor Gene in Type 2 Diabetes Mellitus Patients ofKashmir Valley

“…This feature has been reported in cases of isolated ethnic groups [7][8][9][10][11]and among underprivileged groups in developed countries [12]. NsiIpolymorphism at exon 8 of INSR gene has been associated with arterial hypertension [13]. Analysisof exon 3 of INSR gene demonstrates four possible regions subject to genetic variation with a potential of five polymorphisms: a non-synonymous transition (T↔C) in codon 233 [14], a synonymous substitution at codon 234 (C↔T) [15], a synonymous change at codon 276 (G↔A), and two possible repeats just 5΄of exon 3 [16].…”

A Two-Stage Matched Case–Control Study on Multiple Hypertensive Candidate Genes in Han Chinese

“…Previous studies had reported that an association of polymorphisms in intron 9 and exon 8 of INSR are associated with hypertension. 38,39 A Chinese study suggested a mutation in exon 17 contributing to hypertension. 40 In this study, we investigated 31 SNPs across the INSR gene and identified a novel SNP of rs17254521 in intron 2 which is associated with hypertension.…”

Analysis of the Association of Preeclampsia with Polymorphisms of the <i>INS</i>, <i>INSR </i>and <i>IRS1 </i>Genes in Mexican Women

“…As the placental insulin receptor exhibits low affinity for its ligand in preeclampsia and gestational hypertension [33] , we analyzed the Nsi I polymorphism of INSR , which has been associated with hypertension in Chinese and Australian subjects [18,19] . In addition, it was hypothesized that hypertension-associ- [18] .…”

“…As the placental insulin receptor exhibits low affinity for its ligand in preeclampsia and gestational hypertension [33] , we analyzed the Nsi I polymorphism of INSR , which has been associated with hypertension in Chinese and Australian subjects [18,19] . In addition, it was hypothesized that hypertension-associ- [18] . In our study, the genotypic and allelic distributions of the Nsi I polymorphism did not differ significantly between the normotensive and preeclampsia groups, which suggests that this polymorphism is not associated with the phenotype of preeclampsia without hyperinsulinemia.…”

“…Pst I (rs3842752) and Mae III (rs689) in the insulin gene (INS) [12,13] , Nsi I (rs2059806) in the insulin receptor gene (INSR) [14] and Ala513Pro (rs1801276) and Gly972Arg (rs1801278) in the insulin receptor substrate 1 gene (IRS1) [15] . These polymorphisms have been associated with hyperinsulinemia, hypertriglyceridemia, hypertension, obesity, insulin resistance, increased serum insulin concentration, decreased insulin receptor activity and impaired endothelial function, but these associations have not been observed in all populations analyzed [16][17][18][19][20][21][22][23][24][25] .…”