Association of a Polymorphism in the Lipin 1 Gene With Systolic Blood Pressure in Men

Abstract

Lipin 1 plays a role in abdominal obesity, insulin resistance, and hypertriglyceridemia. The gene is located at 2p25.1, a susceptibility locus for hypertension. We studied the association of tagging single-nucleotide polymorphisms (SNPs) in the lipin 1 (LPIN1) gene with hypertension and blood pressure. Twelve tagging SNPs from the HapMap database were genotyped using Sequenom MassArray in 268 hypertensive subjects and 407 normotensive controls, of whom 268 matched the cases in age and sex. None of the tagging SNPs were found to be associated with hypertension after correcting for multiple testing, although carriers of the minor allele of rs10520097 had nominally lower odds for hypertension (P = 0.014). After excluding subjects who were on antihypertensive medications, the minor allele of rs10495584 was nominally associated with lower mean systolic and diastolic blood pressures in men (121.1 +/- 14.2 and 76.3 +/- 10.2 mm Hg vs. 127.4 +/- 15.2 and 80.1 +/- 10.5 mm Hg, P = 0.002 and 0.007, respectively), but not in women (P > 0.05). The association of rs10495584 with systolic blood pressure in men remained significant after correcting for multiple testing and adjustment for age, waist circumference, insulin resistance, triglyceride, and high-density lipoprotein (HDL) cholesterol (beta = -0.158, P = 0.005). An analysis of statistically similar SNPs (ssSNPs) in the regions surrounding rs10495584 suggested that its effect may be caused by its high linkage disequilibrium (LD) with the SNP, rs11524, in which the major allele forms an exonic splicing silencer sequence. Our study provides further evidence that lipin 1 may play a role in blood pressure regulation, especially in men.