Association of Two Well-defined Polymorphisms in Leptin and Leptin Receptor Genes with Hypertension and Circulating Leptin: A Meta-analysis

Background and Aims The genes encoding adipose-derived hormone leptin and its receptor (LEPR) are increasingly deemed as hypertension-susceptibility genes. In this meta-analysis, we summarized the association of the II/I polymorphism in leptin gene and Gln223Arg polymorphism in LEPR gene with hypertension and circulating leptin. Methods PubMed and Embase were systematically searched. Data extraction and study quality were assessed in duplicate. Statistical analyses were carried out with the STATA software (v. 11.2). Results A total of 11 articles written in English were eligible. Overall analysis identified a significant association between II/I polymorphism I allele and increased risk of hypertension under allelic (odds ratio; 95% confidence interval; P: 1.48; 1.06–2.08; 0.022) and homozygous genotypic (2.27; 1.20–4.29; 0.012) models. The magnitude of the association for II/I polymorphism I allele with hypertension was substantiated in Asians and for essential hypertension under both genetic models. Overall and subgroup analyses failed to reveal any significance for the association between the Gln223Arg polymorphism and hypertension risk. Carriers of Gln223Arg polymorphism Gln/Gln genotype had significantly higher circulating leptin than the Arg/Arg genotype carriers (weighted mean difference; 95% confidence interval; P: 1.61 ng/mL; 0.02–3.20; 0.047), and this significance persisted in essential hypertension subgroup (1.69 ng/mL; 0.02–3.35; 0.047). There were low probabilities of publication bias for the above comparisons. Conclusions Our findings support the contributory role of the II/I polymorphism in leptin gene in the pathogenesis of hypertension, and this role was more evident in Asians and for essential hypertension.