CTLA4, PTNP22, and FOXO3A gene variants as genetic biomarkers for co-occurrence of type 1 diabetes and autoimmune thyroid diseases in the Polish population.

INTRODUCTION

Genetic predisposition is a common determinant of autoimmune endocrinopathies, particularly type 1 diabetes (T1D) and autoimmune thyroid disease (AITD). Although their coexistence is frequent, the underlying genetic background is not fully understood.

OBJECTIVES

We aimed to identify genetic polymorphisms predictive of an increased risk for co‑occurring T1D and AITD, and to assess their potential impact on glycemic control.

PATIENTS AND

METHODS

We genotyped 5 selected polymorphisms (rs3087243 and rs231775 in the CTLA4 gene; rs12730735 in the PTPN22 gene; and rs2802292 and rs9400239 in the FOXO3A gene) in 277 patients with T1D. Clinical data on thyroid status, the presence of thyroid antibodies, treatment, and metabolic control were analyzed.

RESULTS

Thyroid disorders, mostly Hashimoto hypothyroidism, were diagnosed in 32.9% of the patients. As many as 75% required L‑thyroxine (mean thyroid‑stimulating hormone level, 2.15 IU/l). Among thyroid peroxidase- and thyroglobulin‑positive patients, 81.6% and 75%, respectively, had a prior diagnosis of a thyroid disorder. The GG genotype of rs3087243 (CTLA4) conferred a higher risk of hypothyroidism and other thyroid diseases. The GG variant of rs2802292 (FOXO3A) was associated with a reduced prevalence of thyroid disease in family history. Carriers of the AG genotypes in rs3087243 and rs231775 (CTLA4), as well as the GG genotype in rs2802292 (FOXO3A), showed a lower probability of achieving diabetes control, particularly with longer disease duration. However, the CT genotype of rs12730735 (PTPN22) increased the likelihood of achieving glycemic control.

CONCLUSIONS

CTLA4 polymorphisms were associated with an elevated risk of a thyroid disease and poorer glycemic control; FOXO3A showed a dual role, that is, protective against familial thyroid disease but unfavorable for glycemic regulation; and the PTPN22 variant improved glycemic control. Genetic profiling may improve risk assessment and management in patients with T1D.