Investigation of MIF gene promoter variations and their haplotypes in the Alzheimer disease in Turkish population

Abstract

In Alzheimer’s disease, which is characterized by amyloid plaques and neurofibrillary tangles in the brain tissue, many components such as acute phase proteins, cytokines, and proteases contribute to the progression of the disease or are part of the pathological process. The macrophage migration inhibitory factor (MIF) gene encodes a cytokine, which is secreted by lymphocytes, and has a role in the pathogenesis of autoimmune/inflammatory diseases such as rheumatoid arthritis. The purpose of this study to investigate the association between Alzheimer disease and MIF gene promoter polymorphisms. The 205 patients with Alzheimer disease (AD) and 130 age-sex matched healthy individuals were investigated in terms of MIF -173 G/C and MIF −794 CATT polymorphisms. The genotyping of MIF -173 G/C was determined using the RT-PCR method. MIF-794 CATT polymorphism was analyzed using PCR and DNA Sequencing. In terms of binary genotypes and haplotypes, the 5/5-GC (p = 0.004), 6/7-GG (p = 0.02) and, 6/6-GG (p = 0.026) binary genotypes, and 5-C (p = 0.003), 7-G (p = 0.026) and 6-G (p = 0.025) haplotypes were differed significantly between the patients and the controls. This is the first study investigating the relationship between AD and MIF in terms of different genotypes, haplotypes and, alleles. The fact that the binary genotype and allele distributions are significantly different between the patient and control group, suggests that this MIF variants may play a role in the pathogenesis of AD.

Keywords:

• Alzheimer
• cytokine
• inflammation
• MIF
• polymorphism

Acknowledgement

The authors are grateful to Durdane Bekar Aksoy, and,Volkan Solmaz for collecting the samples.

Author contributions

Design: KS, AR; collection of data: KS, AR; Genetic analysis and interpretation of data: KS, AR; literature review: KS writing of article: KS; revision of paper: KS, AR

Disclosure statement

The authors declare that they do not have any conflict of interest.

Ethical approval

Blood samples from volunteers were used for the study. The study was carried out in accordance with the Declaration of Helsinki. The study protocol and all procedures were approved by the Tokat Gaziosmanpasa University Clinical Research Ethics Committee (15-KAEK-019).

Informed consent

Written informed consent was obtained from all participants included in the study.

Additional information

Funding

The necessary funding for this study was provided by Tokat Gaziosmanpasa University Scientific Research Projects (Project Number: 2015/68).