線粒體TXNRD2和ME3基因風險評分與特定的原發性開角型青光眼表型相關聯

Ophthalmology Volume 130, Number 7, July 2023

中文摘要

該研究旨在調查基於TXNRD2和ME3基因變異的遺傳風險評分（genetic risk scores, GRS）是否與原發性開角型青光眼（POAG）的特定臨床特徵相關聯。

研究人員利用全基因組關聯研究（GWAS）數據識別與POAG風險相關的單核苷酸多態性（SNP）在TXNRD2和ME3基因區域中。他們選擇了互相獨立的SNP子集，通過計算每個個體携帶的風險等位基因數目來構建GRS。研究參與者包括POAG患者和對照個體。

作者評估了GRS與POAG相關的各種臨床結果之間的關聯性，例如POAG診斷的概率、最高治療眼內壓（IOP）和副中央視野損失的患病率。他們發現，較高的TXNRD2 GRS與POAG診斷的概率增加相關，而較高的ME3 GRS則與POAG患者中副中央視野損失 (paracentral visual field loss)的患病率增加相關。然而，在診斷年齡或青光眼手術需求等其他臨床指標方面並沒有明顯的相關性。

該研究表明，涉及線粒體功能和氧化應激調節的TXNRD2和ME3基因的遺傳變異可能對POAG的發展和嚴重程度有所貢獻。這些發現突出了遺傳風險評分在個體風險分層和POAG診斷和治療中的個性化應用的潛力。

English Abstract

Title :

Mitochondrial TXNRD2 and ME3 Genetic Risk
Scores Are Associated with Specific Primary
Open-Angle Glaucoma Phenotypes

This study aimed to investigate whether genetic risk scores (GRSs) based on variants in the TXNRD2 and ME3 genes are associated with specific clinical features of primary open-angle glaucoma (POAG).

The researchers used genome-wide association study (GWAS) data to identify single nucleotide polymorphisms (SNPs) associated with POAG risk in the TXNRD2 and ME3 gene regions. They selected a subset of SNPs that were independent of each other and constructed GRSs for each individual by summing the number of risk alleles they carried. The study participants included patients with POAG and control individuals.

The authors assessed the association between GRSs and various clinical outcomes related to POAG, such as the odds of POAG diagnosis, maximum treated intraocular pressure (IOP), and prevalence of paracentral visual field loss. They found that higher GRSs for TXNRD2 and ME3 were associated with increased odds of POAG diagnosis, higher GRSs for TXNRD2 were associated with higher mean maximum treated IOP, while higher GRSs for ME3 were associated with a higher prevalence of paracentral visual field loss in patients with POAG. However, there were no significant associations with other clinical measures, such as age at diagnosis or need for glaucoma surgery.

The study suggests that genetic variants in the TXNRD2 and ME3 genes, which are involved in mitochondrial function and oxidative stress regulation, may contribute to the development and severity of POAG. The findings highlight the potential use of genetic risk scores for individual risk stratification and personalized approaches in the diagnosis and treatment of POAG.