Evaluation of the prevalence of alleles and genotypes of the Gly482Ser polymorphism of the PPARGC1A gene and their effect on kidney function in obese patients

THE AIM: to study the genetic aspects of metabolically healthy and metabolically complicated obesity in Uzbek women - the prevalence of polymorphisms of the PPARGC1A Gly482Ser gene, as well as to assess its relationship with the functional state of the kidneys, clinical, metabolic, hormonal parameters.
PATIENTS AND METHODS: The study involved 224 obese Uzbek women, who were divided into 2 groups: group 1 consisted of 133 women with metabolically complicated obesity, and group 2 consisted of 91 women with metabolically healthy obesity. The control group consisted of 45 healthy women with representative data. In the observation groups, anthropometric parameters, blood pressure, and body composition were determined - the amount of fluid in the body, the visceral obesity index, fat mass, the proportion of active cell mass, the musculoskeletal mass index, and the body water content were studied. We also studied biochemical analyses and the lipid spectrum, the levels of leptin, insulin, cystatin C and uromodulin, IL-6, alpha-TNF, CRP in blood serum, gradations of microalbuminuria in urine, calculated GFR for cystatin C and creatinine, and compared the obtained indicators. The results of all the above studies were compared with the frequency of occurrence of Gly and Ser allele genotypes, GlyGly, GlySer, and SerSer genotypes of the Gly482Ser polymorphism of the PPARGC1A gene in all groups.
RESULTS: When studying the functional state of the kidneys, depending on the occurrence of genotypes of the Gly482Ser polymorphism of the PPARGC1A gene in the MOO group, the following was found. Serum creatinine and cystatin C levels in carriers of the SerSer genotype in the MOO group were significantly higher than in carriers of the GlySer and GlyGly genotypes, as well as in carriers of the SerSer genotype in the comparison groups; the highest MAU and the lowest GFR were found, calculated on the basis of both uromodulin and creatinine and cystatin. When studying the distribution of genotypes depending on the gradation of MAU, the following was revealed. The prevalence of the SerSer genotype in the MOO group is consistent with an increase in the MAU graduation rate. On the contrary, the frequency of occurrence of the GlyGly genotype was higher in patients in the group with optimal MAU. In the MZO group, the SerSer genotype was more common with a slightly increased MAU. On the contrary, the prevalence of the GlyGly genotype decreased with an increase in the MAU graduation rate.
CONCLUSION. Thus, when analyzing the frequency of alleles and genotypes of the Gly482Ser polymorphism of the PPARGC1A gene, depending on the degree of obesity in the groups, the following was revealed. The Ser allele has an aggressive character in relation to an increase in BMI and the development of MOO, and the Gly allele of this polymorphism has demonstrated a protective character in relation to the development of MOO. The SerSer genotype was significantly more common in the MOO group with grade III obesity, while the GlyGly genotype was significantly more common in the control group. Consequently, in the MOO group, the prevalence of the Ser allele and the SerSer genotype of the Gly482Ser polymorphism of the PPARGC1A gene corresponded to an increase in BMI. In the MHO group, the prevalence of the Ser allele and the SerSer genotype of this polymorphism increased in accordance with an increase in BMI. In this group, the prevalence of the Gly allele and the GlyGly genotype decreased, as opposed to an increase in BMI. It was also found that the SerSer genotype of the Gly482Ser polymorphism of the PPARGC1A gene has a pathogenetic significance in the deterioration of the functional state of the kidneys in both phenotypes of obesity, while the GlyGly genotype, on the contrary, has a protective effect on the progression of this patholo

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