The Association of TIMP-1 Serum Level and Genetic Polymorphisms in Type II Diabetes Mellitus Patients: A Novel Case-Control Study

Abstract

     Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia due to decreased insulin secretion, deficient insulin action, or both. DM includes type 1 and type 2. Type 2 diabetes mellitus (T2DM) is primarily caused by insulin resistance, decreased insulin secretion, and increased glucose production. Tissue inhibitors of metalloproteinase-1 (TIMP-1) play a crucial role in extracellular matrix remodeling, which is essential for maintaining skin integrity and promoting wound healing. This study aimed to investigate the association between TIMP-1 genetic variants and their serum levels with the susceptibility to the disease and the development of skin problems in T2DM patients. This study, conducted from November 2023 to April 2024, involved 83 T2DM patients and 75 healthy controls, aiming to investigate the TIMP-1 serum level and determine TIMP-1 single nucleotide polymorphisms (SNPs) rs4898 and rs5953060 frequencies. Results showed higher TIMP-1 levels in the T2DM group (1.83±0.04 vs. 1.66±0.03pg/ml, respectively). Genotyping revealed an increased percentage of TC, CC genotypes, and C allele frequencies for rs4898, and CC genotype and C allele for rs5953060 in the T2DM group (42.17%, 33.73%, and 55.0% for rs4898, 24.10%, and 44.0% for rs5953060). Pairwise linkage disequilibrium analysis between the two SNPs demonstrated that rs4898 had a strong LD with rs5953060 (D’=0.95). Haplotype reconstruction yielded three common two-SNP haplotypes in T2DM versus controls, with none reaching statistical significance (CG:42.6% vs. 38.0% TG:52.2% vs. 54.0%, and TC:3.6% vs. 8.0%, respectively, all P>0.05). Although the TC haplotype showed a non-significant protective trend. In conclusion, TIMP-1 serum levels and the TC, CC/C of rs4898, and CC/C of rs5953060 may be risk factors for skin lesions and susceptibility to T2DM.