Supplementary Material for: Association of Leptin Gene -2548 G/A Polymorphism with Obesity: A Meta-Analysis

<b><i>Background:</i></b> A common single-nucleotide polymorphism identified in the 5′-untranslated region of the leptin gene (LEP -2548 G/A polymorphism) may be associated with obesity, but the existing research findings are inconsistent, so we conducted this meta-analysis. <b><i>Methods:</i></b> Medline, Embase and ISI Web of Science databases were searched to identify relevant studies. Meta-analysis of the total and subgroup populations was conducted using allelic, additive, dominant and recessive models, and odds ratios and their 95% confidence intervals were calculated in a fixed-effect model if no heterogeneity (evaluated as I² statistic) existed. Otherwise, a random-effects model was adopted. Subgroup analysis was performed by ethnicity. Meta-regression and the HETRED analysis were used to explore the potential sources of between-study heterogeneity. Egger's test and influence analysis were conducted to evaluate the publication bias and study power, respectively. <b><i>Results:</i></b> The final selection enrolled 9 studies, including 2,988 subjects (1,372 obese subjects and 1,616 controls). No significant association was identified between the LEP -2548 G/A polymorphism and obesity for all genetic models in the overall population and Caucasians. We found a significant association with allelic, additive and dominant models for subjects of mixed race from South America. Notwithstanding, this significance should be treated cautiously for it is based on a rather small sample (788 involved subjects). <b><i>Conclusions:</i></b> In total, the combined analysis of data from current and published studies suggested that the LEP -2548 G/A polymorphism does not contribute to the development of obesity, despite the fact that a significant association exists in a small subgroup from South America. Further studies are needed to elucidate the relationship.

<b><i>背景:</i></b> 在瘦素基因（leptin gene）的5′-非翻译区（5′-untranslated region, 5′-UTR）中发现的常见单核苷酸多态性（single-nucleotide polymorphism, SNP）——LEP -2548 G/A多态性，可能与肥胖存在关联，但现有研究结论并不一致，因此本研究开展了此项荟萃分析。<b><i>方法:</i></b> 检索MEDLINE、Embase及Web of Science数据库以筛选相关研究。采用等位基因模型、加性模型、显性模型及隐性模型对总人群及亚组人群进行荟萃分析；若无异质性（以I²统计量评估），则采用固定效应模型计算比值比（odds ratio, OR）及其95%置信区间（95% confidence interval, 95%CI），反之则采用随机效应模型。按种族进行亚组分析，采用Meta回归及HETRED分析探索研究间异质性的潜在来源；使用Egger检验及影响力分析分别评估发表偏倚及研究效力。<b><i>结果:</i></b> 最终共纳入9项研究，涉及2988名受试者（其中肥胖受试者1372名，对照人群1616名）。在整体人群及高加索人群中，LEP -2548 G/A多态性与肥胖在所有遗传模型下均未发现显著关联。南美混血人群中，该多态性在等位基因、加性及显性模型下与肥胖存在显著关联，但由于该亚组样本量较小（仅788名受试者），该结果需谨慎解读。<b><i>结论:</i></b> 综合当前已发表研究的合并数据分析结果显示，尽管南美小样本亚组中存在显著关联，但LEP -2548 G/A多态性并未参与肥胖的发生发展。仍需开展进一步研究以阐明二者的具体关联。