Neuropsychiatric Disease and Treatment (Apr 2021)
Association Analysis of Polymorphisms in BIN1, MC1R, STARD6 and PVRL2 with Mild Cognitive Impairment in Elderly Carrying APOE ϵ4 Allele
Abstract
Yue Wu,1,* Jiajun Yin,2,* Bixiu Yang,3 Li Tang,4 Wei Feng,5 Xiaowei Liu,1 Xingfu Zhao,1 Zaohuo Cheng1 1Department of Geriatric Psychiatry, The Affiliated Wuxi Mental Health Center with Nanjing Medical University, Wuxi, Jiangsu Province, People’s Republic of China; 2Brain Science Basic Laboratory, The Affiliated Wuxi Mental Health Center with Nanjing Medical University, Wuxi, Jiangsu Province, People’s Republic of China; 3Department of Clinical Psychology, The Affiliated Wuxi Mental Health Center with Nanjing Medical University, Wuxi, Jiangsu Province, People’s Republic of China; 4Department of General Psychiatry, The Affiliated Wuxi Mental Health Center with Nanjing Medical University, Wuxi, Jiangsu Province, People’s Republic of China; 5Department of Social Prevention and Control, The Affiliated Wuxi Mental Health Center with Nanjing Medical University, Wuxi, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zaohuo ChengDepartment of Geriatric Psychiatry, The Affiliated Wuxi Mental Health Center with Nanjing Medical University, 156 Qianrong Road, Wuxi, 214151, Jiangsu Province, People’s Republic of ChinaTel +86 510 830 30359Fax +86 510 830 12201Email [email protected]: Apolipoprotein (APOE) ϵ4 is recognized as an independent risk factor for mild cognitive impairment (MCI). However, not everyone with the ϵ4 allele develops MCI, suggesting that other susceptibility genes exist. This study aimed to identify MCI susceptibility genes, including BIN1, MC1R, STARD6, and PVRL2, in elderly Han Chinese and to verify their association with APOE ϵ4 allele in MCI onset.Methods: To determine whether polymorphisms in BIN1 (rs6733839, rs7561528), MC1R (rs2228479), STARD6 (rs10164112), and PVRL2 (rs6859) occurred in elderly MCI patients carrying APOE ϵ4 allele, we carried out a case–control study including 285 MCI patients and 326 healthy controls.Results: Statistically significant differences in the proportion of APOE ϵ4 carriers, and BESCI, ADAS-cog, and CNT scores existed between the NC and MCI groups (all P < 0.01). Frequencies of the rs10164112 T and rs6859 A alleles were significantly higher in the latter than in the former (P = 0.01; 0.029). However, no significant differences in allele and genotype distribution of BIN1 (rs6733839, rs7561528) and MC1R (rs2228479) existed between samples in our two groups (all P > 0.05). When stratified by APOE ϵ4 status (carriers/non-carriers), genotype frequencies of BIN1 rs7561528, STARD6 rs10164112, and PVRL2 rs6859 among the four groups (NCϵ4+, NCϵ4-, MCIϵ4+, MCIϵ4-) were significantly different. Additionally, our results suggest a significant association between MCI and BIN1 rs7561528, STARD6 rs10164112, and PVRL2 rs6859 (all P< 0.05) in elderly carriers.Conclusion: This suggests that among the Han Chinese, MCI in elderly APOE ϵ4 carriers may be related to the BIN1 (rs7561528), STARD6 (rs10164112) and PVRL2 (rs6859). Genotype AA of rs7561528 and TT of rs10164112 might be protective factors against MCI in elderly APOE ϵ4 carriers.Keywords: mild cognitive impairment, BIN1, MC1R, STARD6, PVRL2, APOE, polymorphism, association analysis
