Polymorphism of the HMGA2 gene in Polish children and adolescents with short stature and diverse growth hormone secretion

HMGA2 is one of the common genes strongly associated with adult and childhood height. Some studies have also linked this gene to growth hormone deficiency (GHD). This study aimed to investigate polymorphic variants of the HMGA2 gene in Polish children and adolescents with short stature and GHD. Study cohort consisted of 157 children with short stature, including 111 with GHD and 46 with normal growth hormone (GH) secretion. The control group consisted of 142 healthy children of normal height. High-resolution melting (HRM) was used to screen for sequence variants and Sanger sequencing was performed to identify the detected changes. No variants were identified in the coding sequence of the HMGA2 gene. However, two known polymorphisms were observed in intron 3: the G insertion (rs3834468) and the T > A substitution (rs73115423). The statistical analysis of these allele frequencies comparing all short stature children versus controls revealed no significant differences for both polymorphisms studied. However, for rs73115423 within the short stature group, children with GHD had over 3 times lower. A allele frequency than those with normal GH secretion, and the difference was statistically significant (p = 0.042). For rs3834468 no differences were identified within the short stature group. Our findings do not support a definitive role of HMGA2 in the pathogenesis of short stature in Polish children and adolescents. However, they highlight a potential involvement of this gene in the complex mechanisms regulating the somatotropic axis, particularly in relation to GH secretion.