The contribution of the polymorphism of MMR 12 (rs652483) and PPARG (rs1801282) genes to the formation of NAFLD in obese patients


DOI: https://dx.doi.org/10.18565/therapy.2022.10.79-88

Shulkina S.G., Erbes P.E., Smirnov E.N.

Academician E.A. Wagner Perm State Medical University of the Ministry of Healthcare of Russia
Abstract. The increase in the incidence of non-alcoholic fatty liver disease (NAFLD) among people of working age is due to the large influence of environmental factors, while the role of the genetic aspect in the formation and progression of this disease is debatable.
The purpose. To study the frequency of occurrence of allele pairs by polymorphic loci of matrix metalloproteinase MMP12 (rs652483) genes and gamma receptor activated by peroxisome proliferator PPARG (rs1801282) and to determine the role of genes in the formation of NAFLD in obese women and compare with practically healthy women in Perm.
Material and methods. The study included 100 obese patients who were divided into groups: group 1 (n=50) – patients without NAFLD (average age 43,3±5,6 years); group 2 (n=50) – patients with established NAFLD (average age 45,3±3,2 years). The control group consisted of 100 healthy women from Perm. Single nucleotide polymorphic variants of genes were determined by the method of allele-specific polymerase chain reaction using sets of genes MMP12 (rs 652483), PPARG (rs1801282).
Results. Carrying the Pro12Pro genotype of the PPARG gene increases the risk of obesity by 2 times (χ2=5,31, p=0,02, OR 2,05), carrying the Pro12Ala genotype reduced the risk of obesity and NAFLD by 1,7 times (χ2=5,89, p=0,04, OR 0,58). Carrying the PPARG genotype Pro12Pro increases the risk of developing NAFLD in obese patients by 2,5 times. Carrying the polymorphism of the Ala12Ala genotype reduced the risk of obesity by 9 times (χ2=4,23; p=0,04; OR 0,11). Carriers of the Ala12Ala genotype were associated with an increase in IGF-1 levels (p=0,024), carriers of the Pro12Pro genotype with an increase in TG levels (p=0,018). The associations of the carrier of the polymorphic position of the MMR12 gene with an increase in the waist/hip ratio (p=0,02), cystatin C (p=0,01) and MCP-1 (p=0,004) were obtained.
Conclusions. In the female population carrying the PPARG gene polymorphism (rs1801282) of the Ala12Al genotype reduces the risk of obesity and metabolic disorders, carrying the Pro12 Pro genotype increases the risk of obesity and NAFLD. The carrier of the polymorphism of the MMR 12 gene (rs 652438) in women is associated with the development of abdominal obesity and systemic inflammatory response.
Keywords: monocyte chemoattractant protein 1, PPARG, ММР12, insulin-like growth factor 1, non-alcoholic fatty liver disease, genes
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About the Autors

Sofia G. Shulkina, Dr. med. habil., professor of the Department of polyclinic therapy, Academician E.A. Wagner Perm State Medical University of the Ministry of Healthcare of Russia. Address: 614000, Perm, 26 Petropavlovskaya Str. E-mail: shulkina-s@mail.ru. ORCID: https://orcid.org/0000-0002-1686-3885
Polina E. Erbes, assistant at the Department of polyclinic therapy, Academician E.A. Wagner Perm State Medical University of the Ministry of Healthcare of Russia. Address: 614000, Perm, 26 Petropavlovskaya Str. E-mail: erbespolin@gmail.com. ORCID: https://orcid.org/0000-0003-3241-098Х
Elena N. Smirnova, Dr. med. habil., professor, head of the Department of endocrinology and clinical pharmacology, Academician E.A. Wagner Perm State Medical University of the Ministry of Healthcare of Russia. Address: 614000, Perm, 26 Petropavlovskaya Str. E-mail: elenasm2001@mail.ru. ORCID: https://orcid.org/0000-0003-2727-5226


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