Abstract
OBJECTIVE: To investigate the genotypic and allelic association of Src homology 2 B adapter protein 1 (SH2B1) gene polymorphisms with type 2 diabetes mellitus (T2DM) in Jordanian patients. PATIENTS AND METHODS: Three hundred patients were screened, but only 200 adult Jordanian patients diagnosed with T2DM (53.5% male and 46.5% female) have participated in this study. Blood samples were collected from both patients and healthy individuals for DNA extraction according to well-established procedures. Exon 1 and exon 9 of the SH2B1 gene were sequenced using an efficient and sensitive DNA sequencing method in order to identify specific single nucleotide polymorphisms (SNPs) in the SH2B1 gene associated with T2DM. Genetic and haplotype correlation analysis was performed for the chosen SNPs to detect any association if existent. In addition, SNPStats Web Tool and Hardy-Weinberg equilibrium (HWE) analyses for the genotype distribution were used. The significance was determined according to the P-value, and the level of significance taken as P < 0.05. The normality of the data distribution was statically analysed by the Shapiro-Wilk test with a P-value >0.05. Also, the patient's characteristics and clinical data about all participants were mentioned. RESULTS: Two novel variations were present in the SH2B1 gene in Jordanian patients with T2DM: c.827C>G and c.2026G>A, and previously reported five SNPs: rs146946750, rs565131715, rs370302573, rs143212778, rs200470848. Our results showed a strong genetic association of rs565131715 SNP polymorphism within the SH2B1 gene in T2DM patients (χ (2) test, P < 0.001). Additionally, rs143212778 SNP presented a genetic correlation with T2DM patients (χ (2) test, P = 0.035) as compared to control individuals. GTACG haplotype of SH2B1 has a highly significant association with responders (P< 0.0001). CONCLUSION: Our findings indicated a strong association between the rs565131715 polymorphism and the risk of T2DM among the Jordanian population. Moreover, our data showed that the rs143212778 polymorphism significantly elevated the danger of T2DM among this population. This study reveals the first data regarding the SH2B1 gene polymorphisms in Jordanian patients of Arab descent with diabetes.