Role of MT1A Polymorphism and Environmental Mercury Exposure on the Montreal Cognitive Assessment (MoCA)

Abstract

Jintana Sirivarasai,1 Kanchaporn Chaisungnern,2 Pachara Panpunuan,3 Suwannee Chanprasertyothin,4 Sirintorn Chansirikanjana,3 Piyamitr Sritara3 1Graduate Program in Nutrition, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Master of Science Program in Food and Nutritional Toxicology, Institute of Nutrition, Mahidol University, Bangkok, Thailand; 3Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 4Research and Innovation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Jintana SirivarasaiGraduate Program in Nutrition, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 RAMA 6 Road, Ratchatavee District, Bangkok, 10400, ThailandTel [phone]Fax [phone]Email [email protected]: Many age-related structural and functional changes in the brain have important consequences. Long-term exposure to mercury and the impact of functional polymorphisms of metal-regulating proteins such as metallothioneins (MTs) can result in neurological-neurobehavioral effects in elderly individuals. Therefore, the aims of this study are to examine the associations between biomarkers of mercury exposure and cognitive impairment and to investigate the effect of the rs8052394 single nucleotide polymorphism (SNP) of the potential modifier gene MT1A on different domains of the Montreal Cognitive Assessment (MoCA).Materials and Methods: We studied 436 participants aged ≥ 55 years from the Electricity Generating Authority of Thailand study. They underwent a physical examination, an extensive cognitive assessment with the MoCA (cutoff < 26 points), and a biochemical analysis related to diabetes and dyslipidemia. The blood mercury level was determined by inductively coupled plasma mass spectrometry. Genotyping of the MT1A rs8052394 SNP was performed by the restriction fragmentation length polymorphism method.Results: The mean age of the study population was 58.8± 3.01 years, and most had ≥ 12 years of education (75.7%). The primary study finding was that the prevalence of mild cognitive impairment (MCI) in older Thai adults was 39.7%. The frequency distributions of the G allele of the rs8052394 SNP of the MT1A gene were significantly associated with the total and sub-domain MoCA scores. The prevalence of MCI was significantly associated with increased age, hypertriglyceridemia, hyperhomocysteinemia, the third tertile of blood mercury concentration, and the rs8052394 variant genotype of MT1A (P values for all odds ratios < 0.05).Conclusion: These findings suggested that neurocognitive effects associate with mercury exposure and genetic susceptibility in toxicokinetics. Public health strategies can be used to implement as a comprehensive action plan to educate vulnerable populations on how to reduce mercury exposure. Concurrently, impact of such genetic predisposition requires replication for identifying and protecting susceptible individuals from mercury toxicity.Keywords: MT1A, genetic variations, blood mercury, mild cognitive impairment

Keywords

• mt1a
• genetic variations
• blood mercury
• mild cognitive impairment