Fan Wei, Li Shangwei, Huang Zhongying, Chen Qiong
Center of Reproductive Medicine, The West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China,
J Assist Reprod Genet. 2014 Feb;31(2):173-84. doi: 10.1007/s10815-013-0155-2. Epub 2013 Dec 19.
The HLA-G 14-bp insertion/deletion polymorphism had been inconsistently associated with recurrent miscarriage (RM) risk. We examined the association by performing a meta-analysis.
Eligible articles were searched in PubMed, EMBASE and CNKI without language limitation. We included all the articles about two or more miscarriages associated with HLA-G 14-bp polymorphism. The odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed by the STATA10.0 software.
17 studies were included, representing 1786 cases and 1574 controls. The current meta-analysis showed that 14-bp polymorphism was not associated with RM risk in all genetic models and allele contrast(+14 bp vs. -14 bp: OR = 1.13; 95% CI, 0.96,1.32; +14 bp/+14 bp vs. -14 bp/-14 bp: OR = 1.16, 95% CI, 0.85, 1.59; +14 bp/-14 bp vs. -14 bp/-14 bp: OR = 1.21, 95% CI, 0.92,1.58; dominant model: OR = 1.33; 95% CI, 0.99,1.78; recessive model: OR = 1.06; 95% CI, 0.79,1.43). Moreover, a significant heterogeneity was evident across studies. On the other hand, the subgroup analysis demonstrated that there was a significant association between HLA-G 14-bp polymorphism and patients with three or more miscarriages(+14 bp vs. -14 bp: OR = 1.27; 95% CI, 1.04, 1.55; dominant model: OR = 1.52; 95% CI, 1.16, 1.99; and model +14 bp/-14 bp versus -14 bp/-14 bp: OR = 1.51; 95% CI, 1.15, 1.97;).
Our comprehensive meta-analysis indicated that there was insufficient evidence to demonstrate a conclusive association between the HLA-G 14-bp insertion/deletion polymorphism and the risk of RM. But HLA-G 14-bp insertion/deletion polymorphic variation was associated with RM risk in patients with three or more miscarriages. Larger and well-designed studies may eventually provide a better, comprehensive understanding of the association between the HLA-G 14-bp insertion/deletion polymorphism and RM in the future.
HLA - G基因14碱基对插入/缺失多态性与复发性流产（RM）风险的关联并不一致。我们通过进行一项荟萃分析来研究这种关联。
在PubMed、EMBASE和CNKI数据库中检索符合条件的文章，无语言限制。我们纳入了所有关于HLA - G基因14碱基对多态性与两次或更多次流产相关的文章。采用比值比（OR）及95%置信区间（CI）来评估关联强度。使用STATA10.0软件进行统计分析。
纳入17项研究，共1786例病例和1574例对照。当前的荟萃分析表明，在所有遗传模型和等位基因对比中，14碱基对多态性与RM风险无关（+14 bp vs. -14 bp：OR = 1.13；95% CI，0.96，1.32；+14 bp/+14 bp vs. -14 bp/-14 bp：OR = 1.16，95% CI，0.85，1.59；+14 bp/-14 bp vs. -14 bp/-14 bp：OR = 1.21，95% CI，0.92，1.58；显性模型：OR = 1.33；95% CI，0.99，1.78；隐性模型：OR = 1.06；95% CI，0.79，1.43）。此外，各研究间存在显著异质性。另一方面，亚组分析表明，HLA - G基因14碱基对多态性与三次或更多次流产的患者之间存在显著关联（+14 bp vs. -14 bp：OR = 1.27；95% CI，1.04，1.55；显性模型：OR = 1.52；95% CI，1.16，1.99；+14 bp/-14 bp与 -14 bp/-14 bp模型比较：OR = 1.51；95% CI，1.15，1.97）。
我们全面的荟萃分析表明，没有足够的证据证明HLA - G基因14碱基对插入/缺失多态性与RM风险之间存在确凿的关联。但HLA - G基因14碱基对插入/缺失多态性变异与三次或更多次流产患者的RM风险相关。未来，更大规模且设计良好的研究可能最终会对HLA - G基因14碱基对插入/缺失多态性与RM之间的关联提供更好、更全面的理解。
