An exploratory study of the association between SORL1 polymorphisms and sporadic Alzheimer’s disease in the Han Chinese population

Abstract

Feng Zhang,1,2,* Xiaowei Liu,2,* Bailing Wang,3 Zaohuo Cheng,2 Xingfu Zhao,2 Jianzhong Zhu,2 Degang Wang,2 Ying Wang,2 Aiguo Dong,2 Pengpeng Li,2 Chunhui Jin21Mental Health Institute, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, 2Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, 3Qingdao Mental Health Center, Qingdao, Shandong Province, People’s Republic of China*These authors contributed equally to this workAbstract: In previous studies, we reported that the sortilin-related receptor, L (DLR class) A repeats containing (SORL1) gene single nucleotide polymorphisms (SNPs) are associated with the risk of sporadic Alzheimer’s disease (SAD) in the Han Chinese population. To further explore the relationships between SORL1 genetic variants and SAD, we conducted a two-step study. Sequencing analysis in 50 case samples identified 14 SNPs within the promoter and untranslated region of the SORL1 gene. Subsequent genotyping analysis in 106 patients with SAD and 179 healthy controls detected a significant association between the “G” allele of SNP rs1133174 in the 3' untranslated region of the SORL1 gene and SAD risk (odds ratio =1.92, 95% confidence interval [95% CI] =1.28–2.90, adjusted P=0.028). In addition, “G” allele carriers of rs1133174 (GA + GG) have a 2.15-fold increased risk of SAD compared to noncarriers (AA) (adjusted P=0.042). However, no significant positive associations were observed in the other 13 SNPs within the SORL1 gene. These preliminary findings suggest that the SORL1 SNP rs1133174 may be a potential risk locus for SAD in the Han Chinese population.Keywords: SORL1, Alzheimer’s disease, polymorphism, Han Chinese, association