背景:全基因组关联研究(GWAS)表明,3-甲基巴豆酰辅酶A羧化酶(MCCC1)/溶酶体相关膜蛋白3(LAMP3)基因座(rs10513789,rs12637471,rs12493050)的变异可降低高加索人患帕金森病(PD)的风险,中国人和德系犹太人,而二酰甘油激酶θ(DGKQ)基因的rs11248060变体增加了高加索人和汉族人群中PD的风险。然而,他们在马来人中的角色是未知的。因此,本研究旨在调查这些变异与马来人患PD风险的关系.
方法:招募了总共1114名受试者,包括536名PD患者和578名马来人血统的健康对照,并使用Taqman®等位基因区分测定进行基因分型。
结果:MCCC1/LAMP3基因座中rs10513789的G等位基因(OR=0.83,p=0.001)和rs12637471的A等位基因(OR=0.79,p=0.007)与保护作用有关。隐性外显率模型显示了GG基因型对rs10513789和AA基因型对rs12637471的保护作用。未发现与其他MCCC1/LAMP3rs12493050变体或与DGKQ(rs11248060)变体的PD相关。在PD诊断时,四种变异与年龄之间没有发现显着关联。
结论:MCCC1/LAMP3变体rs10513789和rs12637471在马来人群体中具有抗PD的保护作用。
BACKGROUND: Genome-wide association studies (GWAS) have shown that variants in the 3-methylcrotonyl-CoA carboxylase (MCCC1)/lysosome-associated membrane protein 3 (LAMP3) loci (rs10513789, rs12637471, rs12493050) reduce the risk of Parkinson\'s disease (PD) in Caucasians, Chinese and Ashkenazi-Jews while the rs11248060 variant in the diacylglycerol kinase theta (DGKQ) gene increases the risk of PD in Caucasian and Han Chinese cohorts. However, their roles in Malays are unknown. Therefore, this
study aims to investigate the association of these variants with the risk of PD in individuals of Malay ancestry.
METHODS: A total of 1114 subjects comprising of 536 PD patients and 578 healthy controls of Malay ancestry were recruited and genotyped using Taqman® allelic discrimination assays.
RESULTS: The G allele of rs10513789 (OR = 0.83, p = 0.001) and A allele of rs12637471 (OR = 0.79, p = 0.007) in the MCCC1/LAMP3 locus were associated with a protective effect against developing PD in the Malay population. A recessive model of penetrance showed a protective effect of the GG genotype for rs10513789 and the AA genotype for rs12637471. No association with PD was found with the other MCCC1/LAMP3 rs12493050 variant or with the DGKQ (rs11248060) variant. No significant associations were found between the four variants with the age at PD diagnosis.
CONCLUSIONS: MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population.