Analysis of molecular genetic markers of connective tissue dysplasia

Introduction. Connective tissue dysplasia (CTD) is a hereditary, multifactorial condition characterized by impaired development of connective tissue during the embryonic and postnatal periods. This impairment results from genetically determined defects in the formation, maturation, and metabolism of cells and the extracellular matrix. The aim of this study was to investigate the associations of three polymorphic variants of the ADAMTS5 gene with CTD in general, and with specific phenotypic features of CTD.

Materials and Methods. A cross-sectional study was conducted. The study included 181 participants (35 males, 19.3%, 146 females, 80.7%) with a mean age of 21.9 with a standard deviation of 2.9 years. At the first stage, all participants underwent a clinical examination, and signs of CTD were assessed using the Kadurina T.I. score, as modified by Tyurin A.V. The subsequent stage involved a molecular genetic analysis. Statistical data processing was performed using Excel 2024 and GraphPad Prism 8 software packages.

Results. The clinical examination, utilizing quantitative scoring methods, revealed signs of CTD in 130 subjects (71.8%). A comparative analysis of the allele and genotype frequency distributions for the ADAMTS5 gene loci (rs226794, rs9978597, and rs2830585) revealed the following significant associations: the A allele and AA genotype of rs226794 with the presence of internal organ hernias (p=0.015 and p=0.007, respectively); the T allele and TT genotype of rs9978597 with CTD (p=0.003 and p=0.004, respectively); and the T allele and TT genotype with skin hyperelasticity (p=0.03 and p=0.03, respectively) and hypotension (p=0.015 and p=0.02, respectively).

Conclusion. Thus, the polymorphic variant rs226794 of the ADAMTS5 gene is a risk marker for the development of internal organ hernias, while rs9978597 is a risk marker for CTD, skin hyperelasticity, and hypotension.

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