BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in 7.5% in urban Asian Indians. Peroxisome proliferator activated receptor gamma2 (PPARgamma2) has been implicated in adipocyte differentiation. Neuropeptide Y (NPY) is also considered as a candidate gene for excess body fat accumulation. The association of PPARgamma2 (Pro12Ala)} and NPY (Leu7Pro) gene polymorphisms with OSA has not been studied in Asian Indians. OBJECTIVE: To study the distribution of PPARgamma2 (Pro12Ala) and NPY (Leu7Pro) polymorphism in Asian Indians with and without OSA. METHODS AND RESULTS: This study was carried out in 252 obese subjects [(body mass index (BMI > 25 kg/m2]; 142 with OSA and 110 without OSA. Measurements included anthropometric and biochemical parameters (fasting blood glucose, lipid profile, various circumferences and skin-fold thicknesses). PPARgamma2 (Pro12Ala) and NPY (Leu7Pro) gene} polymorphisms were studied in all subjects. The frequency of the variant allele (Ala12) of PPARgamma2 gene was significantly higher in subjects with OSA (14.4%) when compared with subjects without OSA (5.5%; chi2= 9.7; p = 0.001). The distribution of the variant allele (Pro7) of NPY gene was comparable in subjects with OSA (3.5%) and without OSA (3.6%; chi2= 0.001, p = 0.94). CONCLUSION: This study reveals a significantly higher frequency of PPARgamma2 (Ala12) allele in obese Asian Indians with OSA when compared to obese Asian Indians without OSA.