Association between the MCP-1 -2518 A > G (rs1024611) polymorphism and susceptibility to type 2 diabetes mellitus and diabetic nephropathy: a meta-analysis.

BACKGROUND: Studies evaluating the association between monocyte chemoattractant protein-1 (MCP-1) -2518 A > G (rs1024611) polymorphism and type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) are contradictory. The present study aims to provide a comprehensive assessment and more reliable estimation of the relationship between the MCP-1 rs1024611 polymorphism and T2DM and DN risk. METHODS: Eligible articles were retrieved from the PubMed, Web of Science, EMBASE, Cochrane, and China National Knowledge Infrastructure databases. The effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained to calculate the summary effect size. Heterogeneity was analyzed by subgroup analysis and meta-regression. Publication bias was tested using funnel plots and Egger's test. RESULTS: In total, sixteen studies were included. Thirteen studies involving 2,363 patients with T2DM and 4,650 healthy controls found no significant association between the MCP-1 rs1024611 polymorphism and T2DM in the overall population. Ethnicity stratification found an association between the GG + GA genotype and decreased T2DM risk in Caucasians (OR = 0.79, 95% CI: 0.66-0.93, P = 0.006; PQ = 0.372). No significant risks were found in the Asian population for any genetic models. Seven studies found an association between the GG + GA genotype and DN risk in the Asian population (OR = 1.37, 95% CI: 1.11-1.71, P = 0.004, PQ = 0.222). No significant risks were found in the Caucasian population with any genetic models. There were no statistically significant differences in genotype distribution between patients with T2DM and DN in Asians or Caucasians. Meta-regression revealed that genotyping method was a major driver of heterogeneity in five genetic models (GG + GA vs. AA: P = 0.032; GG vs. GA + AA: P = 0.028; GG vs. AA: P = 0.035; GG vs. GA: P = 0.041; G vs. A: P = 0.041). CONCLUSION: The MCP-1 rs1024611 polymorphism is associated with susceptibility to T2DM in Caucasians and DN in Asians. Larger, well-designed cohort studies are needed in the future to verify this association.

Association of tag single nucleotide polymorphisms (SNPs) at lncRNA MALAT1 with type 2 diabetes mellitus susceptibility in the Chinese Han population: A case-control study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic, lifelong disease. The molecular mechanisms and pathophysiology of T2DM have not yet been fully elucidated. Dysregulation of the long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) is considered one of the main contributing factors of the dysfunction found in many diseases, including those of the endocrine system. The aim of this study was to investigate the association between lncRNA MALAT1 single nucleotide polymorphisms (SNPs) and T2DM in the Chinese Han population. METHODS: We genotyped three SNPs (rs3200401 C > T, rs619586 A > G, rs11227209 C > G) of the MALAT1 gene, including 571 T2DM patients and 526 controls. The association between different genotypes and the risk of T2DM was analyzed using logistic regression, and the results were expressed by odds ratio (OR) and its 95% confidence interval (95%CI), and then stratified by age, sex, and BMI. P < 0.05 on both sides was considered as statistically significant. RESULTS: We found that the CT + TT genotypes of the rs3200401 polymorphism were significantly associated with an increased risk of T2DM in Chinese Han population (OR = 1.77; 95% CI:1.35-2.33; Padjusted < 0.001), whereas MALAT1 rs619586 AG + GG genotypes were associated with a reduced risk of T2DM (OR = 0.67; 95% CI:0.48-0.94; Padjusted = 0.021). Subsequent stratified analysis showed that compared with the rs3200401 CC genotype, CT + TT genotypes were associated with an increased risk of T2DM in the male, female, age ≥ 65 years, and BMI ≥ 24 subgroups (OR = 1.68, 95% CI:1.10-2.56, Padjusted = 0.016; OR = 1.83, 95% CI:1.27-2.62, Padjusted = 0.001; OR = 1.86, 95% CI:1.38-2.52, Padjusted < 0.001; OR = 2.13, 95% CI:1.45-3.15, Padjusted < 0.001; respectively). Haplotype analysis showed that T-A-C haplotype had a 1.533-fold increased risk of T2DM (95% CI, 1.208-1.945, P < 0.001) and C-G-G was associated with a decreased risk of T2DM. No significant association was found between rs11227209 and T2DM risk (P > 0.05). CONCLUSION: The results suggest that MALAT1 rs619586 and rs3200401 confer susceptibility for T2DM in the Chinese Han population and provide new genetic targets for the treatment of diabetes and its complications in the future.