Variations in human HLA genes associated with Alzheimer's disease

Abstract

Alzheimer’s disease (AD) is a kind of dementia, which is generally characterized by memory loss, confusion, poor judgment, language disturbance, agitation, withdrawal, and hallucinations and other intellectual abilities that could be serious enough to interfere with daily life. (Förstl H et al., 1999) It is a chronic disease up to now cannot be cured and efficiently slowed and prevented. In the past decade, several studies has been carried out to discover the possible association of HLA allele to Alzheimer’s disease as to establish a possible biomarker for the early diagnostic of the disease. However, these research were performed using low resolution HLA typing (two-digit) that only can distinguish a specific group of alleles for example HLA-A2. Higher resolution typing reaching to a level of specific allele (four digit, amino acid level) using technique of NGS could help to establish a more confident association of HLA with AD with higher specificity. Up to date, the association of specific allele of HLA to AD has not been well studied and investigated. In this research project, it is aimed to study the possible association of HLA class II allele and late onset Alzheimer’s disease (LOAD) in Chinese ethnic population in Hong Kong with the use of next generation sequencing technique. Associations of specific alleles of HLA-DQB1*03:01, HLA-DQB1*03:03, HLA-DQB1*03:05, HLA-DQB1*05:01, HLA-DQB1*05:03, HLA-DQB1*06:01 was focused on in this project. Allele frequency of the HLA-DQB1*06:02 was found elevated with significance in Alzheimer’s disease patients. (P=0.0219, Odd ratio 2.2936 with 95%CI 1.1078 –4.7487) .It suggests that there is association the allele to AD and possibility of this particular allele increases the risks for AD in the Chinese population.