Associations Between the T280M and V249I SNPs in CX3CR1 and the Risk of Age-Related Macular Degeneration.
Associations Between the T280M and V249I SNPs in CX3CR1 and the Risk of Age-Related Macular Degeneration.
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DOI：
10.1167/iovs.15-16830
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发表时间：
2015-08
影响因子：
4.4
通讯作者：
Rui Zhang;Li-yuan Wang;Yafeng Wang;Chang-rui Wu;Chun-ling Lei;Ming-xu Wang;Le Ma
中科院分区：
文献类型：
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作者：
Rui Zhang;Li-yuan Wang;Yafeng Wang;Chang-rui Wu;Chun-ling Lei;Ming-xu Wang;Le Ma
目的 多项研究表明，CX3CR1 基因中两个常见的单核苷酸多态性 (SNP) T280M 和 V249I 会影响年龄相关性黄斑变性 (AMD) 的风险。本研究的目的是将所有已发表的关于这两种变异与 AMD 易感性之间关系的数据结合起来进行荟萃分析，以阐明这种关联。方法 在 MEDLINE、EMBASE 和 ISI Web of Science 中搜索所有关于 AMD 与 T280M 和 V249I 变体之间关系的合格研究。计算等位基因频率、纯合子、第二共显性基因型和显性基因型模型中每个 SNP 的合并比值比 (OR) 和 95% 置信区间 (CI)，以评估这种关联的强度。结果 本荟萃分析共涉及 8 项研究的 3017 例 AMD 病例和 4096 例对照。 T280M 和 V249I SNP 在等位基因（T 与 C：OR = 1.43，95% CI：1.06-1.91；A 与 G：OR = 1.25，95% CI：1.01-1.55）和纯合模型（TT 与 CC：OR = 2.11，95% CI：1.01-1.55）中均表现出与 AMD 风险增加的显着相关性： 1.00-4.43；AA 与 GG：OR = 1.27，95% CI：1.00-1.61），而共显性基因型模型没有观察到显着相关性。此外，显示这两个变异之间高度连锁不平衡的研究表明，与中度连锁不平衡组相比，这些 SNP 与 AMD 风险之间的联系明显更强。结论 报告了纯合子状态下 CX3CR1 中 T280M 和 V249I 变异与 AMD 易感性增加之间存在关系的重要证据。需要进一步的研究来证实这些发现。
PURPOSE Two common single nucleotide polymorphisms (SNPs) in the CX3CR1 gene, T280M and V249I, have been reported to affect the risk of age-related macular degeneration (AMD) in several studies. The aim of the present study was to combine all published data on the relationship between these two variants and AMD susceptibility in a meta-analysis to clarify this association. METHODS MEDLINE, EMBASE, and ISI Web of Science were searched for all eligible studies on the relationship between AMD and T280M and V249I variants. The pooled odds ratio (OR) with 95% confidence intervals (CIs) for each SNP in the allele frequency, homozygote, second codominant genotype, and dominant genotype models were calculated to evaluate the strength of this association. RESULTS A total of 3017 AMD cases and 4096 controls from eight studies were involved in this meta-analysis. Both T280M and V249I SNPs exhibited significant associations with increased risk of AMD in the allele (T versus C: OR = 1.43, 95% CI: 1.06-1.91; A versus G: OR = 1.25, 95% CI: 1.01-1.55) and homozygous models (TT versus CC: OR = 2.11, 95% CI: 1.00-4.43; AA versus GG: OR = 1.27, 95% CI: 1.00-1.61), while no significance association was observed for the codominant genotype model. Moreover, studies showing high linkage disequilibrium between these two variants demonstrated a significantly stronger connection between these SNPs and AMD risk, compared with the moderate linkage disequilibrium group. CONCLUSIONS Significant evidence for a relationship between T280M and V249I variants in CX3CR1 in the homozygote state with increased susceptibility to AMD was reported. Further studies are needed to confirm these findings.