Sex-Specific Associations of MIR137 Polymorphisms With Schizophrenia in a Han Chinese Cohort

Jingwen Yin; Xudong Luo; Qian Peng; Susu Xiong; Dong Lv; Zhun Dai; Jiawu Fu; Ying Wang; Yaxue Wei; Chunmei Liang; Xusan Xu; Dandan Zhang; Lulu Wang; Dongjian Zhu; Xia Wen; Xiaoqing Ye; Zhixiong Lin; Juda Lin; You Li; Jiafeng Wang; Guoda Ma; Keshen Li; Yajun Wang

doi:10.3389/fgene.2021.627874

Sex-Specific Associations of MIR137 Polymorphisms With Schizophrenia in a Han Chinese Cohort

Front Genet. 2021 Feb 23:12:627874. doi: 10.3389/fgene.2021.627874. eCollection 2021.

Authors

Jingwen Yin^{1

2

3

4}, Xudong Luo¹, Qian Peng¹, Susu Xiong¹, Dong Lv¹, Zhun Dai¹, Jiawu Fu⁵, Ying Wang¹, Yaxue Wei¹, Chunmei Liang⁵, Xusan Xu⁵, Dandan Zhang¹, Lulu Wang¹, Dongjian Zhu¹, Xia Wen⁵, Xiaoqing Ye¹, Zhixiong Lin¹, Juda Lin¹, You Li⁵, Jiafeng Wang⁶, Guoda Ma^{5

7}, Keshen Li^{5

7}, Yajun Wang⁷

Affiliations

¹ Department of Psychiatry, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
² Center for Cognitive and Brain Sciences, Institute of Collaborative Innovation, University of Macau, Taipa, China.
³ Department of Psychology, Faculty of Social Sciences, University of Macau, Taipa, China.
⁴ Institute of Neurology, Guangdong Medical University, Zhanjiang, China.
⁵ Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
⁶ Maternal and Children's Health Research Institute, Shunde Maternal and Children's Hospital, Guangdong Medical University, Foshan, China.
⁷ Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

Abstract

Objective: To investigate the effects of microRNA-137 (MIR137) polymorphisms (rs1198588 and rs2660304) on the risk of schizophrenia in a Han Chinese population. Methods: Schizophrenia was diagnosed according to the DSM-5. Clinical symptoms and cognitive functions were assessed with the Positive and Negative Symptom Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS), respectively. The polymorphisms were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 1,116 patients with schizophrenia and 1,039 healthy controls. Results: Significant associations were found between schizophrenia and MIR137 in the distributions of genotypes (p = 0.037 for rs1198588; p = 0.037 for rs2660304, FDR corrected) and alleles (p = 0.043 for rs1198588; p = 0.043 for rs2660304, FDR corrected) of two SNPs. When the population was stratified by sex, we found female-specific associations between MIR137 and schizophrenia in terms of genotype and allele distributions of rs1198588 (χ ² = 4.41, p = 0.036 and χ ² = 4.86, p = 0.029, respectively, FDR corrected) and rs2660304 (χ ² = 4.74, p=0.036 and χ ² = 4.80, p = 0.029, respectively, FDR corrected). Analysis of the MIR137 haplotype rs1198588-rs2660304 showed a significant association with schizophrenia in haplotype T-T [χ ² = 4.60, p = 0.032, OR = 1.32, 95% CI (1.02-1.70)]. Then, significant female-specific associations were found with the haplotypes T-T and G-A [χ ² = 4.92, p = 0.027, OR = 1.62, 95% CI (1.05-2.50); χ ² = 4.42, p = 0.035, OR = 0.62, 95% CI (0.39-0.97), respectively]. When the TT genotype of rs1198588 was compared to the GT+GG genotype, a clinical characteristics analysis also showed a female-specific association in category instances (t = 2.76, p = 0.042, FDR corrected). Conclusion: The polymorphisms within the MIR137 gene are associated with susceptibility to schizophrenia, and a female-specific association of MIR137 with schizophrenia was reported in a Han Chinese population.

Keywords: MIR137; polymorphism; rs1198588; rs2660304; schizophrenia.