中国人群胰岛素依赖性糖尿病HLA-DR基因多态性的Meta分析

Meta-analysis of the association of HLA-DR polymorphism with IDDM in Chinese population

目的:综合评价中国人群HLA鄄DR基因多态性与胰岛素依赖性糖尿病穴IDDM雪的关联性。方法:以IDDM组和健康对照组的各HLA鄄DR等位基因频数(基因型频数、单倍型频数)分布的OR值为统计量。全面检索相关文献,应用Meta分析对血清学分型和基因分型研究的结果进行一致性检验和数据合并,并评估发表偏倚。结果:①血清学分型水平上,HLA鄄DR3和DR9等位基因,DR3/DR4和DR3/DR9杂合子是中国人群IDDM的危险基因穴或基因型雪(P<0.05),合并OR值分别为5.08,1.59,26.74和10.74。而HLA鄄DR2,DR5,DR7,DR12是中国人群IDDM的保护基因(P<0.05),合并OR值分别为0.65、0.57、0.52和0.40;②基因分型水平上,HLA鄄DRB1觹0301,DRB1觹04,DRB1觹0404和DRB1觹0405等位基因是中国人群IDDM的危险基因(P<0.05),合并OR值分别为5.53,2.12,2.40和2.33;单倍型DRB1觹0301/DQA1觹0301/DQB1觹0201和DRB1觹0405/DQB18觹0302,基因型DRB1觹0405/DRB1觹0405和DRB1觹0405/DRB1觹04是中国人群IDDM的危险单倍型穴或基因型雪(P<0.05),合并OR值分别为6.57,14.85,8.08和1.90;而HLA鄄DRB1觹0406,DRB1觹0408,DRB1觹06,DRB1觹07,DRB1觹08,DRB1觹1301,DRB1觹14和DRB1觹16是中国人群IDDM的保护基因(P<0.05),合并OR值分别为0.39,0.11,0.17,0.56,0.33,0.14,0.28和0.39。?

Objective: To evaluate the relationship between genetic polymorphism of HLA-DR and insulin-dependent diabetes mellitus (IDDM) in Chinese population. Methods: Odds ratios (OR) of HLA-DR alleles(genotype, haplotype) distributions in IDDM patients against healthy controls were analysed. All the relevant studies were identified, poorly qualified studies were eliminated, and the risk of publication bias was evaluated. The Meta-analysis software, REVMAN4.2, was applied for investigating heterogeneity among individual studies and summarizing across studies. Results: On the level of serology, HLA-DR3, DR9, DR3/DR4 and DR3/DR9 were the risky alleles (genotype)(P<0.05) and their pooled odds ratios were 5.08,1.59,26.74 and 10.74, respectively; but HLA-DR2, DR5, DR7, and DR12 were protective alleles(P<0.05), with pooled odds ratios of 0.65, 0.57, 0.52 and 0.40, respectively. On the level of DNA,HLA-DRB1*0301, DRB1*04, DRB1*0404 and DRB1.0405 were the risky alleles(P<0.05)whose pooled odds ratios were 5.53, 2.12, 2.40 and 2.33, respectively; DRB1*0301/DQA1*0301/DQB1*0201, DRB1*0405/DQB1*0302, DRB1*0405/0405 DRB1*0405/DRB1*04 were risky haplotypes (genotype) (P<0.05), and their pooled odds ratios were 6.57,14.85,8.08 and 1.90, respectively; but HLA-DRB1*0406, DRB1*0408, DRB1*06, DRB1*07, DRB1*08, DRB1*1301, DRB1*14 and DRB1*16 were protective alleles(P<0.05), their pooled odds ratios being 0.39,0.11,0.17,0.56,0.33,0.14,0.28 and 0.39, respectively. Conclusion: In Chinese population (across the land of China), some HLA-DR alleles (genotype, haplotype) are associated with IDDM, and the associations are very different from those found in other non-Chinese populations.