Association of Genetic polymorphisms of EDN1 gene and Endothelin-1 level in patients with type 2 diabetes mellitus in the Jordanian population

Abstract

Endothelin-1 (ET-1) is one of the most potent vasoconstrictors, encoded by the endothelin-1 (EDN1) gene. It has been shown to play an important role in different diseases including Diabetes Mellitus (DM). Various single nucleotide polymorphisms (SNPs) in the EDN1 gene are related to microvascular complications of type 2 diabetes mellitus (T2DM) such as retinopathy, neuropathy and nephropathy. This study aims to determine the association between two selected EDN1 gene polymorphisms (rs2071942 G > A, rs5370 G > T) and T2DM in the Jordanian population, also to measure the level of ET-1 in T2DM. The samples were collected from the National Center of Diabetes, Endocrinology, and Genetics- Amman, Jordan, including 97 patients with T2DM and 80 healthy individuals. PCR-RFLP was used for SNPs genotyping. ET-1 level was determined using IQELISA kits. The univariate analysis for both SNPs didn't show statistically significant differences in the genotype or allele frequencies among T2DM cases as well as in controls. The same results were obtained regarding ET-1 concentration. The subgroup analysis by sex showed that the genotype and allelic frequencies of rs5370, rs2071942 G/A polymorphisms were not significantly different in males and females. Multivariate Analysis adjusted for various confounders didn't express statistical significance difference for occurrences of both SNPs. However, height and gender showed to be significant risk factors for occurrences of heterozygote alleles in both SNPs. On the other hand, the duration of diabetes has appeared to be related to the recessive allele in rs5370.

Keywords

• Diabetes mellitus type 2
• SNPs
• Endothelin-1
• Gene polymorphism
• Single nucleotide polymorphism
• Susceptibility markers