One Single Nucleotide Polymorphism of the TRPM2 Channel Gene Identified as a Risk Factor in Bipolar Disorder Associates with Autism Spectrum Disorder in a Japanese Population

Naila Al Mahmuda; Shigeru Yokoyama; Toshio Munesue; Kenshi Hayashi; Kunimasa Yagi; Chiharu Tsuji; Haruhiro Higashida

doi:10.3390/diseases8010004

One Single Nucleotide Polymorphism of the TRPM2 Channel Gene Identified as a Risk Factor in Bipolar Disorder Associates with Autism Spectrum Disorder in a Japanese Population

Diseases. 2020 Feb 7;8(1):4. doi: 10.3390/diseases8010004.

Authors

Naila Al Mahmuda^{1

2}, Shigeru Yokoyama¹, Toshio Munesue¹, Kenshi Hayashi³, Kunimasa Yagi³, Chiharu Tsuji¹, Haruhiro Higashida^{1

4}

Affiliations

¹ Department of Basic Research on Social Recognition and Memory, Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan.
² Faculty of Business Administration, Eastern University, Dhaka 1205, Bangladesh.
³ Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8641, Japan.
⁴ Laboratory for Social Brain Studies, Research Institute of Molecular Medicine and Pathobiochemistry, and Department of Biochemistry, Krasnoyarsk State Medical University named after Prof. V. F. Voino-Yasentsky, Krasnoyarsk 660022, Russia.

Abstract

The transient receptor potential melastatin 2 (TRPM2) is a non-specific cation channel, resulting in Ca²⁺ influx at warm temperatures from 34 °C to 47 °C, thus including the body temperature range in mammals. TRPM2 channels are activated by β-NAD⁺, ADP-ribose (ADPR), cyclic ADPR, and 2'-deoxyadenosine 5'-diphosphoribose. It has been shown that TRPM2 cation channels and CD38, a type II or type III transmembrane protein with ADP-ribosyl cyclase activity, simultaneously play a role in heat-sensitive and NAD⁺ metabolite-dependent intracellular free Ca²⁺ concentration increases in hypothalamic oxytocinergic neurons. Subsequently, oxytocin (OT) is released to the brain. Impairment of OT release may induce social amnesia, one of the core symptoms of autism spectrum disorder (ASD). The risk of single nucleotide polymorphisms (SNPs) and variants of TRPM2 have been reported in bipolar disorder, but not in ASD. Therefore, it is reasonable to examine whether SNPs or haplotypes in TRPM2 are associated with ASD. Here, we report a case-control study with 147 ASD patients and 150 unselected volunteers at Kanazawa University Hospital in Japan. The sequence-specific primer-polymerase chain reaction method together with fluorescence correlation spectroscopy was applied. Of 14 SNPs examined, one SNP (rs933151) displayed a significant p-value (OR = 0.1798, 95% CI = 0.039, 0.83; Fisher's exact test; p = 0.0196). The present research data suggest that rs93315, identified as a risk factor for bipolar disorder, is a possible association factor for ASD.

Keywords: ASD; CD38; SNP; TRPM2; bipolar disorder.