Effects of Complement Regulators and Chemokine Receptors in Type 2 Diabetes

Immunol Invest. 2021 Jul;50(5):478-491. doi: 10.1080/08820139.2020.1778022. Epub 2020 Jul 2.

Abstract

CD55 and CD59 are complement regulatory proteins suggested to be related with progression of diabetes and its complications. The stromal cell-derived factor 1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR-4) are chemokine proteins. We aimed to investigate the relation of CD55 and CD59 expression levels and polymorphisms of SDF-1 and CXCR-4 with type 2 diabetes mellitus (T2DM) and its complications. Seventy-five T2DM patients and 73 controls were enrolled. Expression levels of CD55 and CD59 were measured by FACS Calibur; qRT-PCR was used to determine SDF-1 and CXCR-4 gene polymorphisms. CD55 and CD59 expressions in patients with nephropathy, retinopathy and cardiovascular disease were significantly lower than controls. Frequency of CXCR-4 T allele carrying was high in patients and created 1.6 fold risk for the disease (p = .07). CXCR-4 a allele carriers had decreased nephropathy; although there was no statistical significance in carrying CXCR-4 T allele, presence of nephropathy was approximately 2 times higher (p = .254). The nephropathy risk increased 10-fold in CXCR-4 TT genotype carriers (p = .02). All SDF-1 CC genotype carriers had retinopathy, so, it was considered that the CC genotype was effective in retinopathy development (p = .031). For the presence of cardiovascular disease, significant difference was observed for SDF-1 genotypes. Increased cardiovascular risk of 5- and 1.9-fold in SDF-1 T (p = .007) and CXCR-4 T (p = .216) allele carriers, respectively, was observed. We suggest that CD55 and CD59 protein levels and SDF-1 and CXCR-4 have predictive importance in process, complications and tendency of T2DM.

Keywords: CD55; CD59; CXCR-4; SDF-1; Type 2 diabetes.

MeSH terms

  • Aged
  • CD55 Antigens / genetics
  • CD55 Antigens / metabolism*
  • CD59 Antigens / genetics
  • CD59 Antigens / metabolism*
  • Cardiovascular Diseases / genetics*
  • Chemokine CXCL12 / genetics*
  • Diabetes Mellitus, Type 2 / immunology*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Receptors, CXCR4 / genetics*

Substances

  • CD55 Antigens
  • CD59 Antigens
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR4