Investigating Association Level of CXCL12 with its SDF-1α 3′A Genetic Variant and CXCL10 with its-1443 Promoter Polymorphism in Type-1 Diabetes

Abstract

Background: Type-1 diabetes mellitus (T1DM) has been described as an autoimmune and heterogeneous disorder. In the present study, we aimed to examine whether there exists an association between serum CXCL10 (IP-10) level and its promoter polymorphism at position-1443 as an angiostasis alongside CXCL12 and its known SDF-1 3′ A genetic variant as an angiogenesis chemokine in T1DM patients. Methods: Blood specimens were collected from 209 unrelated T1DM patients, as well as from 189 healthy subjects. The DNA samples were extracted from the subjects and analyzed for CXCL10 and CXCL12 polymorphisms by employing PCR-RLFP. The serum concentrations of CXCL10 and CXCL12 were also analyzed with ELISA. Results: Following expert opinion and data analysis, we found significant differences between A/A, A/G, and G/G genotypes with A and G alleles of polymorphisms at position +801 (SDF-1α3′A) in CXCL12. We did not observe an association between CXCL10/-1443 promoter polymorphism and T1DM. In our assessment of promoter polymorphism, both T1DM patients and controls had GG genotype in CXCL10/-1443. When patients were compared with controls, both serum CXCL10 and CXCL12 levels are increased in type 1 diabetes with complications. Levels were not increased in patients without complications. Conclusion: Both CXCL10 and CXCL12 play fundamental roles in T1DM pathogenesis. Only the CXCL12 3′A (SDF-1α3′A) polymorphism is possibly necessary for the pathogenesis of T1DM, while the CXCL10-1443 promoter polymorphism is not.