Association of genetic variants in Leptin, leptin receptor and adiponectin with hypertension risk and circulating Leptin/Adiponectin changes

Abstract

Backgrounds: Hypertension is inheritable, and some candidate genes such as leptin and adiponectin have drawn special concerns.

Objectives: We performed a meta-analysis on the association of 7 genetic variants in genes encoding leptin, leptin receptor and adiponectin with hypertension risk and circulating leptin/adiponectin changes.

Methods: Literature search, report selection and data extraction were performed by two authors independently. Effect sizes are expressed as odds ratio (OR) or standard mean difference (SMD) with 95% confidence interval (CI).

Results: Total 32 reports (7432 cases with hypertension and 9218 controls) were meta-analyzed. Overall analyses indicated that rs7799039 (dominant model: OR = 1.67; 95 % CI: 1.03 to 2.71; P = 0.038) and (TTTC)_n (allelic model: OR = 1.53; 95 % CI: 1.05 to 2.23; P = 0.028) were significantly associated with hypertension risk. Subgroup analyses indicated that hypertension type, race, diabetes, genotyping method and quality score might be potential causes for between-study heterogeneity. Besides rs2241766, no evidence of publication bias existed for the other variants. Carriers of rs7799039-AG genotype had significantly higher leptin concentrations than carriers of rs7799039-GG genotype (SMD = 1.98; 95 % CI: 0.07 to 3.89; P = 0.042). In Mendelian randomization analyses, an increment of leptin concentrations by 1 ng/mL was causally associated with a 25 % significantly increased risk of hypertension (95 % CI: 1.02 to 10+; P < 0.05).

Conclusions: Our findings indicated that leptin gene rs7799039 and (TTTC)_n were potential hypertension-candidacy loci, and importantly high circulating leptin concentrations causally precipitated the development of hypertension.

Keywords: Adiponectin; Hypertension; Leptin; Mendelian Randomization; Meta-analysis.