The Effects of Cytokine Polymorphisms on Predisposition to Microvascular Complications of Diabetes Mellitus: A Meta-Analysis

Abstract

<b><i>Background:</i></b> It is plausible that gene polymorphisms in tumor necrosis factor-α (<i>TNF-α</i>), interleukin (<i>IL</i>)-<i>1</i>, <i>IL-6</i>, <i>IL-8</i>, and <i>IL-18</i> may affect predisposition to microvascular complications of diabetes mellitus (DM), but the results of the so far published studies remain controversial. <b><i>Objectives:</i></b> We conducted this meta-analysis to clarify relationships between <i>TNF-α/IL-1/IL-4/IL-8/IL-18</i> polymorphisms and predisposition to microvascular complications of DM by pooling the findings of eligible studies. <b><i>Methods:</i></b> A comprehensive search of PubMed, Embase, Web of Science, and CNKI was endorsed by us to identify already published studies. Forty-nine studies were found to be eligible for the meta-analyses. <b><i>Results:</i></b> The pooled meta-analyses results showed that genotypic frequencies of <i>TNF-α</i> −238 G/A, <i>TNF-α</i> −308 G/A, <i>TNF-α</i> −1,031 T/C, <i>IL-1A</i> −889 C/T, <i>IL-1B</i> −511 C/T, <i>IL-6</i> −572 G/C, and <i>IL-18</i> −137 G/C polymorphisms among patients with diabetic nephropathy (DN) and controls differed significantly. Moreover, genotypic frequencies of <i>TNF-α</i> −238 G/A and <i>IL-8</i> −251 A/T polymorphisms among patients with diabetic retinopathy (DR) and controls also differed significantly. <b><i>Conclusions:</i></b> This meta-analysis suggested that <i>TNF-α</i> −238 G/A, <i>TNF-α</i> −308 G/A, <i>TNF-α</i> −1,031 T/C, <i>IL-1A</i> −889 C/T, <i>IL-1B</i> −511 C/T, <i>IL-6</i> −572 G/C, and <i>IL-18</i> −137 G/C polymorphisms may affect predisposition of DN. Moreover, <i>TNF-α</i> −238 G/A and <i>IL-8</i> −251 A/T polymorphisms may affect predisposition of DR.