Association of polymorphic markers Arg753Gln in the TLR2 Gene, T-1237C and G2848A in the TLR9 Gene with the risk of developing primary adrenal insufficiency in individuals living in the Moscow Region of the Russian Federation

Background. Primary adrenal insufficiency (PAI) is an endocrine disorder caused by the gradual destruction of all three layers of the adrenal cortex and characterized by insufficient secretion of cortisol and aldosterone. This condition significantly reduces patients’ quality of life, making its timely diagnosis crucial. Autoimmune disorders are the etiological factor in approximately 80% of PAI cases, making the search for predictive markers in innate immune genes one of the most promising areas for predicting the odds of developing PAI. Aims — to study the associations between single nucleotide polymorphisms in the TLR2 and TLR9 genes and the development of PAI. Methods. The study included 222 individuals: 72 patients with PAI and 150 controls. For the study, DNA was isolated from venous blood and subsequently analyzed using real-time PCR with fluorescently labeled probes. Statistical analysis of the results was performed using Fisher’s exact test (Fi), the χ² test, the χ² test with Yates’ correction, calculation of the odds ratio and 95% confidence interval. Results. The study revealed that the A allele (p < 0.001) and the heterozygous genotype (p < 0.001) of the rs5743708 polymorphism in the TLR2 gene were associated with the risk of developing PAI. Conversely, the homozygous genotype GG (p < 0.001) reduced the odds of the pathology development by 11-fold. Analysis of the rs352140 single nucleotide polymorphism in the TLR9 gene also demonstrated an association between the A allele (p = 0.030) and the homozygous AA genotype (p = 0.0171) with the odds of developing PAI. Conclusions. Based on the data obtained in this and our previous study, a scheme was proposed that includes four polymorphic markers to predict the odds of developing 1-HH.