INTRODUCTION Although the coexistence of type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) may be attributed to environmental risk factors common for both diseases, a genetic background should also be considered. Data on the role of genetic factors in the development of T2DM in patients with OSA are lacking. OBJECTIVES The study was aimed to evaluate the prevalence of polymorphisms of selected genes that are known to be associated with diabetes or obesity in patients with OSA and concomitant T2DM and to assess these polymorphisms in the context of OSA severity. PATIENTS AND METHODS Consecutive patients with newly diagnosed OSA confirmed by polysomnography underwent genotyping for the following single nucleotide polymorphisms (SNPs): SREBF1 rs11868035, HIF1A rs11549465, APOA5 rs3135506, TCF7L2 rs7903146, and FTO rs16945088. The frequency of genotypes was compared between patients with and without concomitant T2DM and was analyzed with regard to OSA severity. RESULTS A total of 600 patients with newly diagnosed OSA were enrolled to the study. Of these, 121 patients (20.2%) were diagnosed with T2DM (97 men and 24 women; median age, 58 years; range, 52-64 years). The prevalence of T2DM was significantly lower in APOA5 rs3135506 GG homozygotes than in CG heterozygotes (18.8% vs 33.3%, P = 0.02). APOA5 rs3135506 CG heterozygotes were at higher risk for developing T2DM (adjusted odds ratio, 2.64; 95% confidence interval,1.38-5.04; P = 0.003). No significant differences were found for the genotype distribution of the other investigated SNPs. CONCLUSIONS Our study shows a possible link between the polymorphism of the gene encoding APOA5 and T2DM in patients with OSA.