Genetic Determinants of Microvascular Complications of Type 1 Diabetes Mellitus: New Data from a Replication Study

Background: Diabetic retinopathy (DR) and chronic kidney disease (CKD) are among the leading causes of disability in individuals with type 1 diabetes mellitus (T1DM). However, the genetic architecture of these complications remains poorly understood. Genome-wide studies demonstrate significant interpopulation heterogeneity, while candidate gene studies yield conflicting results due to limited power. Independent replication of previously obtained results in separate cohorts, with appropriate intergroup comparisons, is essential for identifying the most significant biomarkers of microvascular complications in T1DM. Purpose: To search for associations of the most significant polymorphic variants rs55703767, rs72831309, rs118124843, rs9344715, rs183937294, rs4293393, rs12917707, rs77924615, rs11864909, rs9622363, rs73885319, rs2523989, rs3825932, rs763361, rs12708716, rs2292239, and rs4948088 with the risk of developing T1DM and its complications-DR and CKD. Methods: The study involved 618 individuals, including 522 patients with T1DM undergoing inpatient treatment at the Endocrinology Research Centre, as well as 96 control individuals without T1DM. Among the T1DM patients, 232 had concurrent CKD and retinopathy, while 80 were free of both microvascular complications. A comparison of allele and genotype frequencies of 17 single-nucleotide polymorphisms (SNPs) was conducted between the T1DM group and the control group, as well as an intergroup comparison between individuals with and without complications. Results: The rs2292239 (ERBB3) locus is associated with an increased risk (p_bonf = 0.001, OR = 2.02), while rs55703767 (COL4A3) is associated with a decreased risk of developing T1DM in general (p = 0.01846, OR = 0.42). rs9344715 (AKIRIN2) is associated with the risk of diabetic nephropathy (p = 0.03996, OR = 1.29), while PDILT variants rs77924615 (OR = 0.57, p_bonf = 0.045) and rs11864909 (OR = 0.41, p_bonf = 0.0105) with DR. Conclusions: The study identified potential genetic markers for the risk of type 1 diabetes and its microvascular complications. The results require further verification in an independent, expanded cohort. Consideration of genetic factors confirmed the independent contribution of the identified variants, supporting their value as promising biomarkers for risk stratification and personalized prevention of T1DM complications.