Association study of MCCC1/LAMP3 and DGKQ variants with Parkinson's disease in patients of Malay ancestry.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2021 Oct

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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. 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. 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. MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population. © 2021. Fondazione Società Italiana di Neurologia.

Citation

Jia Lun Lim, Ebonne Yulin Ng, Shen-Yang Lim, Ai Huey Tan, Zariah Abdul-Aziz, Khairul Azmi Ibrahim, Aroma Agape Gopalai, Yi Wen Tay, Yuganthini Vijayanathan, Tzi Shin Toh, Soo Kun Lim, Ping-Chong Bee, Santhi Datuk Puvanarajah, Shanthi Viswanathan, Irene Looi, Thien Thien Lim, Gaik Bee Eow, Wee Kooi Cheah, Eng-King Tan, Azlina Ahmad-Annuar. Association study of MCCC1/LAMP3 and DGKQ variants with Parkinson's disease in patients of Malay ancestry. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2021 Oct;42(10):4203-4207