Liu Ying, Jin Huipeng, Wei Dong, Li Wenxiu
Ophthalmic function room, Hongqi Hospital Affiliated to Mudanjiang Medical College, Mudanjiang, 157000, Heilongjiang Province, China.
Department of Ophthalmology (three disease areas), Hongqi Hospital Affiliated to Mudanjiang Medical College, Mudanjiang, 157000, Heilongjiang Province, China.
BMC Med Genet. 2020 May 15;21(1):107. doi: 10.1186/s12881-020-01047-5.
The high-temperature requirement factor A1 (HTRA1) gene located at 10q26 locus has been associated with age-related macular degenerative (AMD), with the significantly related polymorphism being (rs11200638, -625G/A), however, above association is not consistent. We investigated a comprehensive analysis to evaluate the correlations between rs11200638 polymorphism and AMD susceptibility thoroughly addressing this issue.
An identification was covered from the PubMed and Wanfang databases until 27th Jan, 2020. Odds ratios (OR) with 95% confidence intervals (CI) were applied to evaluate the associations. After a thorough and meticulous search, 35 different articles (33 case-control studies with HWE, 22 case-control studies about wet/dry AMD) were retrieved.
Individuals carrying A-allele or AA genotype may have an increased risk to be AMD disease. For example, there has a significantly increased relationship between rs11200638 polymorphism and AMD both for Asians (OR: 2.51, 95%CI: 2.22-2.83 for allelic contrast) and Caucasians [OR (95%CI) = 2.63(2.29-3.02) for allelic contrast]. Moreover, a similar trend in the source of control was detected. To classify the type of AMD, increased association was also observed in both wet (OR: 3.40, 95%CI: 2.90-3.99 for dominant model) and dry (OR: 2.08, 95%CI: 1.24-3.48 for dominant model) AMD. Finally, based on the different genotyping methods, increased relationships were identified by sequencing, TaqMan, PCR-RFLP and RT-PCR.
Our meta-analysis demonstrated that HTRA1 rs11200638 polymorphism may be related to the AMD development, especially about individuals carrying A-allele or AA genotype, who may be as identified targets to detect and intervene in advance. Further studies using Larger sample size studies, including information about gene-environment interactions will be necessary to carry out.
位于10q26位点的高温需求因子A1（HTRA1）基因与年龄相关性黄斑变性（AMD）相关，显著相关的多态性为（rs11200638，-625G/A），然而，上述关联并不一致。我们进行了一项综合分析，以全面评估rs11200638多态性与AMD易感性之间的相关性，从而彻底解决这一问题。
截至2020年1月27日，从PubMed和万方数据库中进行检索。采用比值比（OR）及95%置信区间（CI）评估相关性。经过全面细致的检索，共检索到35篇不同的文章（33篇符合哈迪-温伯格平衡的病例对照研究，22篇关于湿性/干性AMD的病例对照研究）。
携带A等位基因或AA基因型的个体患AMD疾病的风险可能增加。例如，rs11200638多态性与亚洲人（等位基因对比的OR：2.51，95%CI：2.22 - 2.83）和白种人（等位基因对比的OR（95%CI）= 2.63(2.29 - 3.02)）的AMD均显著相关。此外，在对照来源方面也检测到类似趋势。为对AMD类型进行分类，在湿性（显性模型的OR：3.40，95%CI：2.90 - 3.99）和干性（显性模型的OR：2.08，95%CI：1.24 - 3.48）AMD中均观察到关联增加。最后，基于不同的基因分型方法，通过测序法、TaqMan法、聚合酶链反应 - 限制性片段长度多态性（PCR - RFLP）法和逆转录 - 聚合酶链反应（RT - PCR）法均确定了相关性增加。
我们的荟萃分析表明，HTRA1 rs11200638多态性可能与AMD的发生发展相关，尤其是对于携带A等位基因或AA基因型的个体，他们可能作为提前检测和干预的目标人群。有必要开展更大样本量的进一步研究，包括基因 - 环境相互作用的相关信息。
