Combined association analysis of interleukin 1-receptor antagonist (IL-1RN) variable number of tandem repeat (VNTR) and Haptoglobin 1/2 polymorphisms with type 2 diabetes mellitus risk

J Diabetes Metab Disord. 2016 Mar 29:15:10. doi: 10.1186/s40200-016-0232-z. eCollection 2015.

Abstract

Background: The polymorphism of Interleukin 1 receptor antagonist gene (IL-1RN), which encodes a natural antagonist of pro-inflammatory cytokines belonging to IL-1 family and Haptoglobin (HP) have been studied in various ethnic groups in association with Type 2 Diabetes Mellitus (T2DM) risk and related complications. However, there was no study available among the Emirati population. Hence, we designed a combined study on IL-1RN and HP polymorphism to evaluate their association with prevalence of T2DM, related complication and hypertension and also its interaction with obesity status among Emirati population.

Methods: IL-1RN and HP genotypes were determined in total 487 Emiratis divided in two groups of T2DM case (n = 271) and healthy controls (n = 215) by polymerase chain reaction (PCR) followed by gel electrophoresis. Gene-gene interaction and polymorphism-obesity interaction were determined by multivariate logistic regression analysis.

Results: We found that the frequencies of IL-1RN*1/*1 and HP2-2 genotypes were significantly higher in cases than control and were associated with increased T2DM risk with an odds ratio (OR) of 1.60 (95 % CI 1.10-2.36) and 1.63 (95 % CI 1.11-2.64), respectively. The association lack any interaction with obesity status. Associations with occurrences of T2DM related complications and hypertension were not observed.

Conclusions: We report an association of IL-1RN and HP polymorphism with T2DM risk independent of each other and of obesity status but no association with related complications and hypertension.

Keywords: Genetic polymorphism; Haptoglobin; Interleukin-1 receptor antagonist; Type 2 Diabetes Mellitus.