Association between the L55M and Q192R polymorphisms of the paraoxonase-1 gene and age-related macular degeneration: a meta-analysis

ABSTRACT Purpose: Paraoxonase-1 activity is associated with age-related macular degeneration. Two polymorphisms (L55M and Q192R) were shown to increase paraoxonase-1 activity and have been implicated in the development of age-related macular degeneration. The results of studies that have examined these polymorphisms are conflicting, showing no effect, as well as increased or decreased risk. Therefore, this meta-analysis was conducted to determine the effect of these polymorphisms on age-related macular degeneration. Methods: PubMed, EBSCO, LILACS, and Scopus databases, as well as and the retrieved bibliographies of publications were searched for case-control studies that examined for paraoxonase-1 polymorphisms and age-related macular degeneration. Data were analyzed using the Comprehensive Meta-Analysis Version 2.2 and the NCSS Statistical Version 2020 software. Genotype distributions were extracted and, depending on the level of heterogeneity, fixed effects or random effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. Results: Overall, for the L55M polymorphism, none of the genetic models demonstrated a significant association. However, for non-Asian populations, a significant association was determined for the heterozygous and dominant genetic models (ORrange=1.24-1.27, p<0.05). For the Asian population, the heterozygous, dominant, and allelic genetic models demonstrated a benefit/protective factor (ORrange=0.29-0.35, p<0.05). For the Q192R polymorphism, none of the genetic models demonstrated a significant association. However, when the cohort was grouped by ethnicity, a significant association was determined in the Asian population for the recessive and allelic genetic models (ORrange=1.63-2.08, p<0.05). However, for the non-Asian population, there was no association observed. Also, there was no identifiable risk when the cohort was stratified into exudative and non-exudative cases. Conclusions: The paraoxonase-1L55M polymorphism increases the risk of developing age-related macular degeneration in non-Asian populations, whereas in Asian populations, the polymorphism exerts a protective effect. However, for the paraoxonase-1 Q192R polymorphism, only the Asian population demonstrated a risk of developing age-related macular degeneration.

摘要
研究目的：对氧磷酶-1（paraoxonase-1）的活性与年龄相关性黄斑变性（age-related macular degeneration, AMD）密切相关。已有研究显示，L55M与Q192R两种多态性位点可增强对氧磷酶-1的活性，且与年龄相关性黄斑变性的发生存在关联。但目前相关研究的结论存在分歧，部分研究未观察到该多态性的影响，另有研究则显示其可升高或降低发病风险。为此，本研究开展此项荟萃分析（meta-analysis），以明确上述两种多态性位点对年龄相关性黄斑变性的关联效应。

研究方法：本研究检索了PubMed、EBSCO、LILACS及Scopus数据库，并对检索到的文献的参考文献列表进行追溯，纳入所有探讨对氧磷酶-1多态性与年龄相关性黄斑变性相关性的病例-对照研究。采用Comprehensive Meta-Analysis Version 2.2及NCSS Statistical Version 2020统计软件进行数据分析。提取各基因型分布数据，并根据异质性检验结果，分别采用固定效应模型或随机效应模型，计算杂合子、纯合子、显性、隐性以及等位基因五种遗传模型的合并比值比（odds ratios, OR）及其95%置信区间（95% confidence intervals, 95% CIs）。

研究结果：整体而言，针对L55M多态性，所有遗传模型均未显示出显著关联。但在非亚洲人群中，杂合子模型与显性模型均检测到显著关联（OR范围：1.24~1.27，p<0.05）。在亚洲人群中，杂合子、显性及等位基因模型均表现出保护效应（OR范围：0.29~0.35，p<0.05）。针对Q192R多态性，所有遗传模型均未显示出显著关联。但按种族分层分析后，亚洲人群的隐性模型与等位基因模型均观察到显著关联（OR范围：1.63~2.08，p<0.05）；而非亚洲人群则未发现此类关联。此外，将研究队列按渗出型与非渗出型年龄相关性黄斑变性分层后，未识别到显著的发病风险差异。

研究结论：对氧磷酶-1 L55M多态性可升高非亚洲人群发生年龄相关性黄斑变性的风险，而在亚洲人群中该多态性则发挥保护作用。但对于对氧磷酶-1 Q192R多态性，仅在亚洲人群中观察到其与年龄相关性黄斑变性的发病风险相关。