Key result
The GIPR rs2302382 polymorphism was associated with type 2 diabetes, and the C-G haplotype was significantly more frequent in healthy controls (OR 1.99; 95% CI 1.44-2.75; p<0.001).
Why the study?
Are GIPR and GLP-1R genetic polymorphisms associated with type 2 diabetes mellitus and incretin levels in Egyptian patients?
Case-Control (n=300)
Are GIPR and GLP-1R genetic polymorphisms associated with type 2 diabetes mellitus and incretin levels in Egyptian patients?
Odds Ratio: 1.99 (95% CI 1.44–2.75)
p-value: p=< 0.001
The GIPR rs2302382 polymorphism and specific haplotypes are associated with an increased risk of type 2 diabetes mellitus in the Egyptian population.
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.
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Shalaby et al. (2017) conducted a case-control in Type 2 diabetes mellitus (n=300). GIPR and GLP-1R genetic polymorphisms vs. Healthy controls was evaluated on Association with Type 2 Diabetes Mellitus (OR 1.99, 95% CI 1.44-2.75, p=< 0.001). The GIPR rs2302382 polymorphism was associated with type 2 diabetes, and the C-G haplotype was significantly more frequent in healthy controls (OR 1.99; 95% CI 1.44-2.75; p<0.001).
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