Association of incretin receptors genetic polymorphisms with type 2 diabetes mellitus in Egyptian patients. (21st September 2017)

• Record Type: Journal Article
• Authors: Shalaby, Sally M.; Zidan, Haidy E.; Shokry, Amira; Saeed, Jehan; El‐Sokkary, Rehab H.
• Is Part Of: Journal of gene medicine. Volume 19:Number 9/10(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-09-21
• Subjects: diabetes mellitus -- GIP -- GLP‐1 -- incretins -- polymorphism; Genetic transformation -- Periodicals; Gene Transfer -- Periodicals; Gene Therapy -- Periodicals; 616.042
• DOI: 10.1002/jgm.2973
• Languages: English
• ISSNs: 1099-498X

Abstract

Abstract: Background: Incretins have opened a new era in type 2 diabetes mellitus (T2DM) pathogenesis. The present study aimed to assess whether there is an association between GIPR rs2302382, GIPR rs1800437 and GLP‐1R rs367543060 polymorphisms with T2DM or not and also to determine the effect of these polymorphisms on gastric inhibitory polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) levels . Methods: One hundred and fifty T2DM patients and 150 healthy controls were included in the study. Polymorphisms of GIPR rs1800437, GIPR rs2302382 and GLP ‐1R rs367543060 were genotyped using restriction fragment length polymorphism (RFLP) ‐ polymerase chain reaction (PCR), multiplex allele‐specific PCR and RFLP‐PCR respectively. GIP and GLP levels were measured by an enzyme‐linked immunosorbent assay. Results: We found a significant association of both the homozygous AA and the minor allele A of GIPR rs2302382 with T2DM. The frequency of haplotype C( rs2302382 ) G( rs1800437 ) was significantly higher in controls than in diabetics; odds ratio (95% confidence interval): 1.99 (1.44–2.75) ( p < 0.001), whereas the haplotype A( rs2302382 ) C( rs1800437 ) was significantly higher in patients than controls. We did not find any association of GLP‐1R rs367543060 polymorphism with T2DM. We found a significant increase in serum total GIP and a significant decrease of GLP‐1 levels in T2DM patients. Conclusions: We reveal for the first time an association between the GIPR rs2302382 polymorphism and T2DM in Egyptians. Yet, there was no significant association of GIPR rs1800437 or GLP‐1R rs367543060 with T2DM risk. The haplotype A ( rs2302382 ) C ( rs1800437 ) was associated with an increased risk of T2DM. Furthermore, there was a significant increase of GIP and a significant decrease of GLP‐1 levels when diabetic patients were compared with controls. An important finding was that there was a relationship between both GIPR rs2302382 and rs1800437 variants and their cognate ligand levels.