BACKGROUND: Obesity is a widespread disease associated with serious complications. Obesity is a risk factor for many chronic diseases. The most common type of obesity is polygenic obesity, the pathogenesis of which involves external and internal factors, including genetic ones.AIM: Search and study of the association of variants of the nucleotide sequence rs9939609 of the FTO gene, rs7903146 of the TCF7L2 gene, rs1799883 of the FABP2 gene, rs1800497 of the DRD2 gene, rs17782313 of the MC4R gene with morbid obesity in women.MATERIALS AND METHODS: Study design is case-control study. The morbid obesity group and the control group were formed from the DNA bank of participants of the international project HAPIEE. Genotyping was performed by PCR-RFLP and real-time PCR (TaqMan probes, Applied Biosystems, USA). Statistical analysis was performed in SPSS software using Pearson’s chi-square test, Fisher’s exact two-tailed test with Yates’ correction for continuity. The significance level was used p<0.05.RESULTS: Morbid obesity group included 192 women (mean age 57.02± .16 years) with BMI over 40 kg/m2, control group included 450 women (mean age 55.44±7.41 years) with normal BMI (18.5-24.9 kg/m2). There were no statistically significant differences between the groups in the frequencies of genotypes and alleles rs7903146 of the TCF7L2 gene, rs1799883 of the FABP2 gene, rs1800497 of the DRD2 gene (p>0.05). In the group of morbid obesity, the proportion of carriers of the TT genotype rs9939609 of the FTO gene was statistically significantly lower, and the AT genotype was significantly higher than in the control group (OR=0.579, 95% CI 0.399-0.840, p=0.004; OR=1.408, 95% CI 1.003- 1.976, p=0.047, respectively). The heterozygous TC genotype rs17782313 of the MC4R gene is statistically significantly more common (OR=1.825, 95% CI 1.257-2.652, p=0.002), while the homozygous TT genotype is less common (OR=0.500, 95% CI 0.346-0.723, p<0.001) in group of morbid obesity compared with the control group.CONCLUSION: Heterozygous genotypes of the rs9939609 of the FTO gene (AT) and rs17782313 of the MC4R gene (TC) are risk genotypes; the homozygous genotype TT of the variants is protective for morbid obesity in women. Single nucleotide variants rs7903146 of the TCF7L2 gene, rs1799883 of the FABP2 gene, and rs1800497 of the DRD2 gene are not associated with morbid obesity in women.