Lack of association between leptin G-2548A polymorphisms and obesity risk: Evidence based on a meta-analysis

Background: The prevalence of obesity is increasing in most industrialized and developing countries. We aimed to investigate the association between leptin (LEP) G-2548A polymorphisms and the risk of obesity.

Methods: We searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases for studies that evaluated the association between LEP G-2548A polymorphisms and obesity risk prior to March 2014. The odds ratio (OR) and its 95% confidence interval (95% CI) were calculated to estimate the risk of obesity. Meta-analysis of subgroup populations and different control sources was conducted using homozygote (AA vs. GG), allelic (A vs. G), dominant (AA+GA vs. GG), recessive (AA vs. GG+GA), and heterozygote (AG vs. GG) models. The heterogeneity of the studies was assessed using χ(2)-tests based on Q-statistics. The pooled ORs were calculated using a random-effects model if there was no heterogeneity; otherwise, a random-effects model was used. Two authors extracted the data independently. The funnel plots, Begg's and Egger's test were used to assess publication bias. All statistical analyses were performed using STATA 12.0 software.

Results: Nine case-controlled publications that evaluated the association between LEP G-2548A polymorphisms and obesity risk, which included 2594 subjects (1235 obesity cases and 1359 controls), were included in our meta-analysis. No significant association between this polymorphism and obesity risk was observed (P>0.05). Significant heterogeneity was detected among the studies. The results of subgroup analysis according to ethnicity and different control groups suggested that LEP G-2548A polymorphisms might increase the obesity risk in African populations in the homozygote (AA vs. GG: OR=2.38, 95% CI=1.15-4.93, P=0.020) and recessive (AA vs. GG+GA: OR=2.03, 95% CI=1.34-3.06, P=0.001) models.

Conclusions: Overall, this meta-analysis indicated that LEP G-2548A polymorphisms are not associated with obesity risk, although significant associations were observed in the homozygote model (AA vs. GG) and the recessive model (AA vs. GG+GA) in Africa populations. Further studies are still needed to validate and confirm this association.