Genetic study of HLA alleles with Alzheimer's disease

Abstract

The risk of Alzheimer disease (AD) increases with age. Itis not curable and can be fatal. The aging population is expanded worldwide, making a huge economy and medical burden in coming decade, especially in China and India. Generally, patients with Alzheimer disease show no symptoms at the preclinical stage. Diagnosis of Alzheimer disease can only be done after the onset of symptoms that based on a set of standard congenital assessments, family history, physiological tests on blood and urine as well as brain scan, so forth so on. It may take around ten years for patient to develop from preclinical stage to the symptom onset, resulting in severe AD. Therefore investigation on the early diagnosis of Alzheimer disease is necessary for future preparation and living arrangement in advance. Effective use of natural nonsteroidal anti-inflammatory drugs (NSAIDs) to delay the symptoms of Alzheimer disease suggested the risk of Alzheimer disease associated with human leukocyte antigen (HLA) gene. Several difference lines of genome wide association studies have also been stated the human leukocyte antigen (HLA) alleles, A2 allele and DR/ DQ allele, play an important role in inflammatory response during the development of both early-onset and late-onset Alzheimer disease, and independent to the apolipoprotein gene. However controversial results were indicated due to allelic polymorphism among different ethnic groups, small size of sample, inclusion criteria and low resolution of HLA typing.

The study aims to examine the association between human leukocyte antigen-A alleles and late-onset Alzheimer disease in Chinese population by HLA typing with the high resolution next generation sequencing technology. According to genome wide association study in Chinese population, HLA-A2, A11, A24 and A33 are the most predominant allele found in various autoimmune disease including Graves’ disease and late-onset Alzheimer disease. 223 patients with late-onset Alzheimer disease and 149 controls were recruited in the study and found that the haplotype HLA-A*02:07 showed protective profile with the late onset Alzheimer disease, which oppose to the evident of HLA-A contribute to the risk of Alzheimer disease. To conclude, it is the significant finding on the protective effect of HLA-A*02:07 in late- onset Alzheimer disease. Additional independent sample sets and larger studies in other ethnic groups will be important to replicate and support the present findings.