State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Mol Cell Endocrinol. 2012 Jul 6;358(1):9-17. doi: 10.1016/j.mce.2012.02.010. Epub 2012 Feb 28.
Genetic association studies on the gene encoding receptor for advanced glycation end products (RAGE) and diabetes mellitus have reported conflicting results. To evaluate the association of RAGE gene four widely-evaluated polymorphisms (T-429C, T-374A, Gly82Ser and G1704T) and diabetes mellitus, a meta-analysis was conducted. A random-effects model was applied irrespective of between-study heterogeneity. There were a total of 5808/3742 (n=14) case-patients/controls (studies) for T-429C, 8259/6935 (n=19) for T-374A, 7029/5266 (n=19) for Gly82Ser, and 2843/3302 (n=13) for G1704T. Overall results detected no significant association of polymorphisms T-429C, T-374A and Gly82Ser with diabetes risk. There was a trend toward an increased risk for alleles 1704T relative to 1704G (odds ratio [OR]=1.09; 95% confidence interval [CI]: 0.98-1.22; I(2)=0). Subgroup analysis by ethnicity indicated that allele 1704T conferred a significantly increased risk in East Asians (OR=1.21; 95% CI: 1.04-1.4; I(2)=0) but not in Caucasians (OR=0.8; 95% CI: 0.6-1.07; I(2)=0), and that by type of diabetes mellitus indicated that association was potentiated exclusively for G1704T with diabetic retinopathy (OR=1.24; 95% CI: 1.01-1.51; I(2)=0). No publication bias was observed. Our results provide convincing evidence regarding the association of RAGE gene 1704T allele with an increased risk of diabetes mellitus, especially diabetic retinopathy. Notably, this effect was more pronounced in East Asians.
对编码晚期糖基化终产物受体（RAGE）基因的基因与糖尿病的遗传关联研究报告结果相互矛盾。为了评估 RAGE 基因四个广泛评估的多态性（T-429C、T-374A、Gly82Ser 和 G1704T）与糖尿病之间的关联，进行了荟萃分析。应用随机效应模型，无论研究间的异质性如何。T-429C 有 5808/3742（n=14）病例-对照（研究），T-374A 有 8259/6935（n=19），Gly82Ser 有 7029/5266（n=19），G1704T 有 2843/3302（n=13）。总体结果未发现多态性 T-429C、T-374A 和 Gly82Ser 与糖尿病风险显著相关。等位基因 1704T 相对于 1704G 有增加风险的趋势（比值比[OR]=1.09；95%置信区间[CI]：0.98-1.22；I(2)=0）。按种族进行的亚组分析表明，等位基因 1704T 使东亚人患糖尿病的风险显著增加（OR=1.21；95% CI：1.04-1.4；I(2)=0），而在白种人中则没有（OR=0.8；95% CI：0.6-1.07；I(2)=0），按糖尿病类型进行的亚组分析表明，这种关联仅对糖尿病视网膜病变的 G1704T 显著增强（OR=1.24；95% CI：1.01-1.51；I(2)=0）。未观察到发表偏倚。我们的结果提供了令人信服的证据，证明 RAGE 基因 1704T 等位基因与糖尿病的风险增加相关，特别是糖尿病视网膜病变。值得注意的是，这种效应在东亚人中更为明显。
