Role of genetic variants in gene encoding lipocalin-2 in the development of elevated blood pressure

Abstract

Introduction: Lipocalin-2 is recently recognised as a biomarker of obesity and inflammation, which are both risk factors for hypertension. We therefore investigated the association of common single nucleotide polymorphisms (SNPs) in the gene encoding lipocalin-2 (LCN2) with elevated blood pressure in Hong Kong Chinese. Methods: Five tagging SNPs were genotyped in 1936 subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) with a median follow-up period of 6.4 years. Elevated blood pressure was defined as ≥130/85 mm Hg or taking anti-hypertensive medication. Results: There were only two haplotypes with frequency of >5%, namely AGATC (45.5%) and GGTCC (41.2%). Haplotype GGTCC was associated with elevated blood pressure at follow-up (OR=1.17 compared to haplotype AGATC, P=0.031 after adjusting for age and sex). Among 1381 subjects without elevated blood pressure at baseline, 321 subjects developed elevated blood pressure at follow-up. Haplotype GGTCC was associated with the development of elevated blood pressure at follow-up (OR=1.30 compared to haplotype AGATC, P=0.011 after adjusting for age, sex, systolic blood pressure, and follow-up duration; OR=1.44, P=0.0015 after further adjusting for other covariates). Among subjects not taking anti-hypertensive medication, carriers of the haplotype GGTCC had higher systolic blood pressure than non-carriers (119.7±16.4 mm Hg vs 117.9±17.3 mm Hg, P=0.043). Conclusion: Our findings suggest, for the first time, that genetic variants in LCN2 may affect blood pressure. Further studies on the role of lipocalin-2 in blood pressure regulation are warranted. Acknowledgement: This study was funded by Hong Kong Research Grant Council grants (HKU7229/01M and HKU7626/07M) and the Sun Chieh Yeh Heart Foundation.