Investigation of Genetic Predisposition of Clusterin Gene (rs9331888) in Pakistani Patients with Type 2 Diabetes Mellitus and Alzheimer’s disease

Abstract

Type 2 Diabetes Mellitus (T2DM) is a disease characterized by insulin resistance and progressive β cell failure, and has several consequences one of which lead in the development of several forms of cognitive dysfunction including Alzheimer’s disease (AD). T2DM and AD shared some common genetic associations which lead to the progression of AD in T2DM patients. This study aims at to investigate the association of genetic predisposition of SNP rs9331888 of Clusterin (CLU) gene and to evaluate the post-transcriptional expression levels of CLU gene in T2DM and AD patients. This was done through genotyping (ARMS-PCR)and through expression analysis (qRT-PCR).In this present study, individuals were recruited with the written informed consent and was selected based on the inclusion and exclusion criteria. Blood samples were collected for T2DM and AD patients from different hospitals. Firstly, genomic DNA and RNA were extracted, synthesis of cDNA was done and afterwards ARMS-PCR and qRT-PCR were performed. An elevated level of expression of CLU gene was observed in AD patients with a significant (p<0.0001) difference from T2DM patients and control subjects. An association of polymorphism of SNP rs9331888 was found between T2DM and AD patients as compared with the control subjects. This study concluded a significant association between T2DM and AD and proposed a potential role of CLU gene with disease susceptibility in T2DM and AD patients but need further justification of the findings, as the sample size was small. In future, this finding would possibly be important in providing benefit in T2DM control and reducing the risk of AD development respectively.