Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, College of Medicine, Institute of Endemic Disease, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi 710061, People's Republic of China.
Br J Nutr. 2012 Jan;107(2):164-9. doi: 10.1017/S0007114511002704. Epub 2011 Jun 23.
Kashin-Beck disease (KBD) is a chronic endemic osteoarthropathy, which mainly occurs in West and Northeast China. Epidemiological studies suggest that Se deficiency is an important environmental factor for the incidence of KBD. Glutathione peroxidase 4 (GPx4) belongs to the glutathione peroxidase family, which is crucial for optimal antioxidant defences. Our purpose is to investigate the putative association between GPx4 polymorphisms and the risk of KBD. Restriction fragment length polymorphism-PCR was used to detect two SNP (rs713041, rs4807542) in 219 cases and 194 controls in Han Chinese subjects, and quantitative analysis for the GPx4 mRNA level was performed by the real-time PCR method. The results revealed that linkage disequilibrium existed in the two SNP. A significant difference was observed in the haplotype A-T (P = 0·0066) of GPx4, which was obviously lower in the KBD cases (0·006 v. 0·032 %). Correlation analysis based on a single locus showed no association between each SNP and KBD risk. Furthermore, the GPx4 mRNA level was dramatically lower in the blood of KBD patients. Overall, our finding indicated GPx4 polymorphisms and decreased mRNA level may be related to the development of KBD in the Chinese population, suggesting GPx4 as a possible candidate susceptibility gene for KBD.
大骨节病（KBD）是一种慢性地方性骨关节病，主要发生在中国西部和东北部。流行病学研究表明，硒缺乏是 KBD 发病的重要环境因素。谷胱甘肽过氧化物酶 4（GPx4）属于谷胱甘肽过氧化物酶家族，对最佳抗氧化防御至关重要。我们的目的是研究 GPx4 多态性与 KBD 风险之间的可能关联。采用限制性片段长度多态性-PCR 检测 219 例病例和 194 例对照中汉族人群的两个 SNP（rs713041、rs4807542），并采用实时 PCR 法对 GPx4 mRNA 水平进行定量分析。结果显示，两个 SNP 存在连锁不平衡。GPx4 的单倍型 A-T（P=0·0066）存在显著差异，KBD 病例明显降低（0·006 v. 0·032%）。基于单一位点的相关分析显示，每个 SNP 与 KBD 风险均无关联。此外，KBD 患者血液中的 GPx4 mRNA 水平显著降低。总之，我们的发现表明 GPx4 多态性和 mRNA 水平降低可能与中国人群 KBD 的发生有关，提示 GPx4 可能是 KBD 的一个潜在候选易感基因。
