Association of hypertension with single nucleotide polymorphisms in the quantitative trait locus for abdominal obesity-metabolic syndrome on chromosome 17

Abstract

Genome scan in Chinese revealed an association of blood pressure with the microsatellite marker D17S1303, which lies in a quantitative trait locus for the abdominal obesity-metabolic syndrome (AOMS2) at 17p12 on chromosome 17. We previously reported that D17S1303 was associated with hypertension and obesity. Therefore, we studied 10 single nucleotide polymorphisms (SNP) within 3 kb of D17S1303. One hundred and eighty hypertensive subjects (91 men, 89 women, age 53712 years) and 180 normotensive matched controls (91 men, 89 women, age 52711) were genotyped using the Sequenom genotyping platform. Allelic frequencies in these Chinese subjects differed from those reported for Caucasians. Three SNPs (rs11656507, rs1357926, rs852319) were homozygous in our subjects. The genotype frequencies of rs852320, rs852321 and rs852322 did not differ between hypertensive and normotensive subjects. However, there were significant differences for rs1525402 (P ¼ 0.048), rs2692343 (P ¼ 0.022), rs2692344 (P ¼ 0.017) and rs2321313 (P ¼ 0.028). A four-locus haplotype comprising G at rs1525402, C at rs2692343, C at rs2692344 and G at rs2321313 was associated with lower systolic blood pressure (P ¼ 0.023) and normotension (P ¼ 0.048). Our results provide further evidence that there is a gene, as yet unidentified, influencing blood pressure in the vicinity of D17S1303 in a quantitative trait locus for abdominal obesity-metabolic syndrome at 17p12.

Single-nucleotide polymorphisms near the microsatellite D17S1303 and the development of hypertension in a 6-year longitudinal study

“…The present results are compatible with our previous findings, 4,5 suggesting that an unidentified gene or a regulatory element influencing the development of hypertension may be found in a region downstream of the microsatellite marker D17S1303. The number of subjects with new onset hypertension was limited, so the sample size or the length of follow-up needs to be increased in future.…”

“…4 Some single nucleotide polymorphisms (SNPs) within a 3 kb region of D17S1303 were associated with hypertension in a case-control study. 5 A recent genome-wide linkage analysis for blood pressure also revealed an association of the microsatellite marker, D17S921 at 17p12 (about 4000 kb downstream from D17S1303) with diastolic blood pressure in pooled Australian and Dutch populations. 6 Therefore, there may be an unidentified gene or regulatory element in the vicinity of this locus that determines blood pressure.…”

“…4,5 Tagging SNPs with r 2 thresholds of 1.0 and minor allele frequencies 40.05 were chosen from the HapMap database on Han Chinese. We selected 65 tagging SNPs that captured 129 SNPs in a region of about 60 kb upstream and 70 kb downstream of the microsatellite, D17S1303.…”

“…Genotyping was performed using the Sequenom MassARRAY system (Sequenom, San Diego, CA, USA). 5 Haploview (version 3.2) was used to test each SNP for Hardy-Weinberg equilibrium (HWE) and assess linkage disequilibrium (LD). The WHAP program was used to test the association of SNPs and haplotypes with the development of hypertension at year 6.…”

Hypertension and genes: perspectives from this journal

“…17 This could potentially lead to the development of new drugs that could target both hypertension and the metabolic syndrome. 18 Also, Guizar-Mendoza et al 19 performed a study to establish the relationship between Gln223Arg polymorphism in the human leptin receptor gene (LEPR) and traits related to obesity in Mexican adolescents. Their study showed that obese adolescents have higher heart sympathetic activity, blood pressure, insulin and leptin levels than non-obese subjects, and furthermore those who were carriers of the Gln223Arg polymorphism of LEPR have sympathetic overactivity and hypertension.…”