Association of insulin gene VNTR INS -23/Hph1 A>T (rs689) polymorphism with type 1 diabetes mellitus in Egyptian children

Background Type1 diabetes mellitus (T1DM) has a multi-factorial pathogenesis; the interplay between genetic susceptibility and environmental factors is thought to provide the fundamental element for the disease. Apart from HLA, more than 50 genetic variants are associated with T1DM. INS -23/Hph1 A>T (rs689) is one of the effective loci with inconsistent reports in the literature. Accordingly, this study was designed to define the frequencies of INS -23/Hph1 A>T polymorphism and its association with T1DM in Egyptian diabetic children and their non-diabetic family members as compared to healthy controls. Methods Using polymerase chain reaction-restriction fragment length polymorphism methodology, analysis of insulin gene VNTR polymorphism was performed for 496 samples (91 patients, 179 parents, 130 siblings, and 96 controls); parents and siblings were apparently healthy. Results INS genotypes and allele frequencies were comparable between patients, non-diabetic siblings, and parents ( p = 0.97 and 0.77, respectively). However, the TT/AT genotype and T allele were over-presented in the three family groups compared to controls ( p = 0.0015 and 0.0029, respectively). Comparing patients to controls, the T allele is considered a risk factor for the development of TIDM (OR 2.56, 95% CI 1.42–4.62, p = 0.0017). INS -23/Hph1 A>T polymorphism showed concordance between patients and their mothers (Kappa = 0.446, p = 0.000) but not with their fathers (Kappa = 0.031, p = 0.765). Conclusions INS -23/Hph1 A>T gene polymorphism was shown to be a risk factor for the development of TIDM. This is in agreement with some and in disagreement with other reports. Studies of risk susceptibility factors have to be carried out locally in each community; results cannot be extrapolated from one ethnic group to another.