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

Lim JL 1 , Ng EY 2 , Lim SY 3 , Tan AH 3 , Abdul-Aziz Z 4 , Ibrahim KA 4 Show all authors , Gopalai AA 1 , Tay YW 1 , Vijayanathan Y 5 , Toh TS 5 , Lim SK 6 , Bee PC 7 , Puvanarajah SD 8 , Viswanathan S 8 , Looi I 9 , Lim TT 10 , Eow GB 11 , Cheah WK 12 , Tan EK 13 , Ahmad-Annuar A 14

Affiliations 

  • 1 Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
  • 2 Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore, Singapore
  • 3 Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 4 Department of Medicine, Hospital Sultanah Nur Zahirah, Kuala Terengganu, Malaysia
  • 5 Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 6 Division of Nephrology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 7 Division of Haematology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 8 Department of Neurology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
  • 9 Department of Medicine and Clinical Research Centre, Hospital Seberang Jaya, Penang, Malaysia
  • 10 Island Hospital, Penang, Malaysia
  • 11 Department of Neurology, Hospital Pulau Pinang, Penang, Malaysia
  • 12 Department of Medicine, Hospital Taiping, Taiping, Perak, Malaysia
  • 13 Department of Neurology, National Neuroscience Institute, Academia, 20 College Road, Level 4, Singapore, 169856, Singapore. [email protected]
  • 14 Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. [email protected]
Neurol Sci, 2021 Oct;42(10):4203-4207.
PMID: 33559030 DOI: 10.1007/s10072-021-05056-x

Abstract

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.

CONCLUSION: MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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