Association of genetic variants in Leptin, leptin receptor and adiponectin with hypertension risk and circulating...

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

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.

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).

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).

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.