Роль полиморфизма rs1801282 гена PPARG в прогнозировании риска развития нарушений углеводного обмена и выборе тактики лечения

1. Глобальный доклад по диабету. Женева: Всемирная организация здравоохранения, 2018. Лицензия: CC BY-NC-SA 3.0 IGO [Global report on diabetes. Geneva: World Health Organization, 2018. License: CC BY-NC-SA (in Russian)].
2. Park KS. The search for genetic risk factors of type 2 diabetes mellitus. Diabetes Metab J. 2011;35(1):12-22. DOI:10.4093/dmj.2011.35.1.12
3. Moore AF, Jablonski KA, McAteer JB, et al. Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program. Diabetes. 2008;57(9):2503-10. DOI:10.2337/db08-0284
4. Zhou K, Donnelly LA, Kimber CH, et al. Reduced-function SLC22A1 polymorphisms encoding organic cation transporter 1 and glycemic response to metformin: a GoDARTS study. Diabetes. 2009;58(6):1434-9. DOI:10.2337/db08-0896
5. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. Под ред. И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. 10-й выпуск. Сахарный диабет. 2021;24(S1):221 [Standards of specialized diabetes care. Eds II Dedov, MV Shestakova, AYu Mayorov. 10th edition. Diabetes mellitus. 2021;24(S1):221 (in Russian)]. DOI:10.14341/DM12802
6. Meirhaeghe A, Tanck MWT, Fajas L, et al. Study of a new PPARGamma2 promoter polymorphism and haplotype analysis in a French population. Mol Genet Metab. 2005,85(2):140-8. DOI:10.1016/j.ymgme.2005.02.004
7. Montagner A, Rando G, Degueurce G, et al. New insights into the role of PPARs. Prostaglandins Leukot Essent Fatty Acids. 2011;85(5):235-43. DOI:10.1016/j.plefa.2011.04.016
8. Yen CJ, Beamer BA, Negri C, et al. Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun. 1997;18;241(2):270-4. DOI:10.1006/bbrc.1997.7798
9. Frederiksen L, Brødbaek K, Fenger M, et al. Comment: studies of the Pro12Ala polymorphism of the PPAR-gamma gene in the Danish MONICA cohort: homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome. J Clin Endocrinol Metab. 2002;87(8):3989-92. DOI:10.1210/jcem.87.8.8732
10. Sarhangi N, Sharifi F, Hashemian L, et al. PPARG (Pro12Ala) genetic variant and risk of T2DM: a systematic review and meta-analysis. Sci Rep. 2020;10(1):12764. DOI:10.1038/s41598-020-69363-7
11. Wang X, Liu J, Ouyang Y, et al. The association between the Pro12Ala variant in the PPARγ2 gene and type 2 diabetes mellitus and obesity in a Chinese population. PLoS One. 2013;8(8):e71985. DOI:10.1371/journal.pone.0071985
12. Tan GD, Neville MJ, Liverani E, et al. The in vivo effects of the Pro12Ala PPARGamma2 polymorphism on adipose tissue NEFA metabolism: the first use of the Oxford Biobank. Diabetologia. 2006;49(1):158-68. DOI:10.1007/s00125-005-0044-z
13. Ho JS, Germer S, Tam CH, et al. Association of the PPARG Pro12Ala polymorphism with type 2 diabetes and incident coronary heart disease in a Hong Kong Chinese population. Diabetes Res Clin Pract. 2012;97(3):483-91. DOI:10.1016/j.diabres.2012.03.012
14. Бирюкова Е.В. Молекулярно-генетические, гормонально-метаболические и клинические аспекты метаболического синдрома. Автореф. дис. … канд. мед. наук. М. 2009 [Biryukova EV. Molekulyarno-geneticheskie, gormonal'no-metabolicheskie i klinicheskie aspekty metabolicheskogo sindroma. Avtoref. dis. … kand. med. nauk. Moscow. 2009 (in Russian)].
15. Мкртумян А.М., Бирюкова Е.В., Маркина Н.В. Молекулярно-генетические особенности, характер метаболизма глюкозы и функция эндотелия у больных метаболическим синдромом русской популяции. Сахарный диабет. 2008;11(4):26-30 [Mkrtumyan AM, Biryukova EV, Markina NV. Molekulyarno-geneticheskie osobennosti, kharakter metabolizma glyukozy i funktsiya endoteliya u bol'nykh metabolicheskim sindromom russkoy populyatsii. Diabetes mellitus. 2008;11(4):26-30 (in Russian)]. DOI:10.14341/2072-0351-5585
16. Chistiakov DA, Potapov VA, Khodirev DS, et al. The PPARGamma Pro12Ala variant is associated with insulin sensitivity in Russian normoglycaemic and type 2 diabetic subjects. Diab Vasc Dis Res. 2010;7(1):56-62. DOI:10.1177/1479164109347689
17. Bystrova AA, Ulitina AS, Kim MV, et al. Genetic Risk Factors of Macrovascular Complications in Patients with Type 2 Diabetes. Kardiologiia. 2017;57(2):17-22.
18. Потапов В.А. Поиск генетических маркеров, определяющих предрасположенность к сахарному диабету типа 2. Автореф. дис. … канд. мед. наук. М. 2010 [Potapov VA. Poisk geneticheskikh markerov, opredelyayushchikh predraspolozhennost' k sakharnomu diabetu tipa 2. Avtoref. dis. … kand. med. nauk. Moscow. 2010 (in Russian)].
19. Чернобривцев П.А., Пищулина С.В., Кишеня М.С. Особенности распределения генотипов и аллелей Rs1801282 гена PPARG у больных метаболическим синдромом в Lонецком регионе. Университетская Клиника. 2017;3(24):56-60 [Chernobrivtsev PA, Pishchulina SV, Kishenya MS. Osobennosti raspredeleniya genotipov i allelei Rs1801282 gena PPARG u bol'nykh metabolicheskim sindromom v donetskom regione. Universitetskaya Klinika. 2017;3(24):56-60 (in Russian)].
20. Mori H, Ikegami H, Kawaguchi Y, et al. The Pro12 -->Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes. Diabetes. 2001;50(4):891-4. DOI:10.2337/diabetes.50.4.891
21. Galbete C, Toledo E, Martínez-González MA, et al. Pro12Ala variant of the PPARG2 gene increases body mass index: An updated meta-analysis encompassing 49,092 subjects. Obesity (Silver Spring). 2013;21(7):1486-95. DOI:10.1002/oby.20150
22. González Sánchez JL, Serrano Ríos M, Fernández Perez C, et al. Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene on adiposity, insulin sensitivity and lipid profile in the Spanish population. Eur J Endocrinol. 2002;147(4):495-501. DOI:10.1530/eje.0.1470495
23. Bhatt SP, Misra A, Sharma M, et al. Ala/Ala genotype of Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-γ2 gene is associated with obesity and insulin resistance in Asian Indians. Diabetes Technol Ther. 2012;14(9):828-34. DOI:10.1089/dia.2011.0277
24. Cole SA, Mitchell BD, Hsueh WC, et al. The Pro12Ala variant of peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with measures of obesity in Mexican Americans. Int J Obes Relat Metab Disord. 2000;24(4):522-4. DOI:10.1038/sj.ijo.0801210
25. Mansoori A, Amini M, Kolahdooz F, Seyedrezazadeh E. Obesity and Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor-Gamma Gene in Healthy Adults: A Systematic Review and Meta-Analysis. Ann Nutr Metab. 2015;67(2):104-18. DOI:10.1159/000439285
26. Tellechea ML, Aranguren F, Pérez MS, et al. Pro12Ala polymorphism of the peroxisome proliferatoractivated receptor-gamma gene is associated with metabolic syndrome and surrogate measures of insulin resistance in healthy men: interaction with smoking status. Circ J. 2009;73(11):2118-24. DOI:10.1253/circj.cj-09-0320
27. Radha V, Vimaleswaran KS, Babu HN, et al. Role of genetic polymorphism peroxisome proliferator-activated receptor-gamma2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: Evidence for heterogeneity. Diabetes Care. 2006;29(5):1046-51. DOI:10.2337/diacare.2951046
28. Hegele RA, Cao H, Harris SB, et al. Peroxisome proliferator-activated receptor-gamma2 P12A and type 2 diabetes in Canadian Oji-Cree. J Clin Endocrinol Metab. 2000;85(5):2014-9. DOI:10.1210/jcem.85.5.6610
29. Kilpeläinen TO, Lakka TA, Laaksonen DE, et al. SNPs in PPARG associate with type 2 diabetes and interact with physical activity. Med Sci Sports Exerc. 2008;40(1):25-33. 
DOI:10.1249/mss.0b013e318159d1cd
30. Lindi VI, Uusitupa MI, Lindstrom J, et al. Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study. Diabetes. 2002;51(8):2581-6.
31. Valeeva FV, Medvedeva MS, Khasanova KB, et al. Association of gene polymorphisms with body weight changes in prediabetic patients. Mol Biol Rep. 2022.
DOI:10.1007/s11033-022-07254-y
32. Исакова Ж.Т., Талайбекова Э.T., Жыргалбекова Б.Ж., и др. Межгенные взаимодействия и вклад полиморфных локусов генов KCNJ11, ADIPOQ, оментина, лептина, TCF7L2 и PPARG в развитие сахарного диабета 2-го типа в кыргызской популяции: исследование по типу случай–контроль с использованием MDR-анализа. Проблемы эндокринологии. 2018;64(4):216-25 [Isakova ZhT, Talaibekova ET, Zhyrgalbekova BZh, et al. Gene-gene interaction and the contribution of polymorphic loci of KCNJ11, ADIPOQ, omentin, leptin, TCF7L2 and PPARG genes in the development of type 2 diabetes mellitus in the Kyrgyz population: a case-control genetic association study using MDR-analysis. Problems of Endocrinology. 2018;64(4):216-25 (in Russian)]. DOI:10.14341/probl8344
33. Hashemian L, Sarhangi N, Afshari M, et al. The role of the PPARG (Pro12Ala) common genetic variant on type 2 diabetes mellitus risk. J Diabetes Metab Disord. 2021;20(2):1385-90. DOI:10.1007/s40200-021-00872-6
34. Al-Naemi AH, Ahmad AJ. Is the rs1801282 (G/C) Polymorphism of PPAR – Gamma Gene Associated with T2DM in Iraqi People? Open Access Maced J Med Sci. 2018;6(3):447-55. DOI:10.3889/oamjms.2018.156
35. Wang F, Han XY, Ren Q, et al. Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population. Chin Med J (Engl). 2009;122(20):2477-82.
36. Meigs JB, Manning AK, Fox CS, et al. Genome-wide association with diabetes-related traits in the Framingham Heart Study. BMC Med Genet. 2007;8 Suppl 1(Suppl 1):S16. DOI:10.1186/1471-2350-8-S1-S16
37. Montagnana M, Fava C, Nilsson PM, et al. The Pro12Ala polymorphism of the PPARG gene is not associated with the metabolic syndrome in an urban population of middle-aged Swedish individuals. Diabet Med. 2008;25(8):902-8. DOI:10.1111/j.1464-5491.2008.02510.x
38. Pattanayak AK, Bankura B, Balmiki N, et al. Role of peroxisome proliferator-activated receptor gamma gene polymorphisms in type 2 diabetes mellitus patients of West Bengal, India. J Diabetes Investig. 2014;5(2):188-91. DOI:10.1111/jdi.12130
39. Hotta K, Kitamoto A, Kitamoto T, et al. Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography. J Hum Genet. 2012;57(5):305-10. DOI:10.1038/jhg.2012.21
40. Oh EY, Min KM, Chung JH, et al. Significance of Pro12Ala Mutation in Peroxisome Proliferator-Activated Receptor-γ2 in Korean Diabetic and Obese Subjects. J Clin Endocrinol Metab. 2000,85(5):1801-4. DOI:10.1210/jcem.85.5.6499
41. Bakhashab S, Filimban N, Altall RM, et al. The Effect Sizes of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants on Type 2 Diabetes Mellitus Risk among the Western Saudi Population: A Cross-Sectional Prospective Study. Genes (Basel). 2020;11(1):98. DOI:10.3390/genes11010098
42. Kruzliak P, Haley AP, Starcevic JN, et al. Polymorphisms of the peroxisome proliferator-activated receptor-γ (rs1801282) and its coactivator-1 (rs8192673) are associated with obesity indexes in subjects with type 2 diabetes mellitus. Cardiovasc Diabetol. 2015;14:42. DOI:10.1186/s12933-015-0197-0 
43. Sikhayeva N, Iskakova A, Saigi-Morgui N, et al. Association between 28 single nucleotide polymorphisms and type 2 diabetes mellitus in the Kazakh population: a case-control study. BMC Med Genet. 2017;18(1):76. DOI:10.1186/s12881-017-0443-2
44. Ben Ali S, Ben Yahia F, Sediri Y, et al. Gender-specific effect of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma-2 gene on obesity risk and leptin levels in a Tunisian population. Clin Biochem. 2009;42(16-17):1642-7. DOI:10.1016/j.clinbiochem.2009.08.019
45. Phani NM, Vohra M, Rajesh S, et al. Implications of critical PPARγ2, ADIPOQ and FTO gene polymorphisms in type 2 diabetes and obesity-mediated susceptibility to type 2 diabetes in an Indian population. Mol Genet Genomics. 2016;291(1):193-204. DOI:10.1007/s00438-015-1097-4
46. Винник Н.И., Куценко Л.А., Куценко Н.Л., и др. Особенности клинической эффективности применения пиоглитазона в комплексной терапии больных с ишемической болезнью сердца на фоне метаболического синдрома. Артериальная гипертензия. 2011;1(15):79-86 [Vinnik NI, Kutsenko LA, Kutsenko NL, et al. Osobennosti klinicheskoi effektivnosti primeneniya pioglitazona v kompleksnoi terapii bol'nykh s ishemicheskoi bolezn'yu serdtsa na fone metabolicheskogo sindroma. Arterial'naya gipertenziya. 2011;1(15):79-86 (in Russian)].
47. Kawaguchi-Suzuki M, Frye RF. Current clinical evidence on pioglitazone pharmacogenomics. Front Pharmacol. 2013;4:147. DOI:10.3389/fphar.2013.00147
48. Hsieh MC, Lin KD, Tien KJ, et al. Common polymorphisms of the peroxisome proliferator-activated receptor-gamma (Pro12Ala) and peroxisome proliferator-activated receptor-gamma coactivator-1 (Gly482Ser) and the response to pioglitazone in Chinese patients with type 2 diabetes mellitus. Metabolism. 2010;59(8):1139-44. DOI:10.1016/j.metabol.2009.10.030
49. Еременко Т.В., Мациевский Н.А., Ворохобина Н.В., и др. Клинический эффект применения тиазолидиндионов у пациентов с нарушениями углеводного обмена при носительстве полиморфизма rs1801282. Ожирение и метаболизм. 2020;17(2):193-9 [Eremenko TV, Matsievskiy NA, Vorokhobina NV, et al. Clinical effect of thiazolidinediones in subjects with disorders of carbohydrate metabolism in case of polymorphism rs1801282. Obesity and metabolism. 2020;17(2):193-9 (in Russian)]. DOI:10.14341/omet9943
50. Blüher M, Lübben G, Paschke R. Analysis of the relationship between the Pro12Ala variant in the PPAR-gamma2 gene and the response rate to therapy with pioglitazone in patients with type 2 diabetes. Diabetes Care. 2003;26(3):825-31. DOI:10.2337/diacare.26.3.825
51. Namvaran F, Azarpira N, Rahimi-Moghaddam P, Dabbaghmanesh MH. Polymorphism of peroxisome proliferator-activated receptor γ (PPARγ) Pro12Ala in the Iranian population: relation with insulin resistance and response to treatment with pioglitazone in type 2 diabetes. Eur J Pharmacol. 2011;671(1-3):1-6. DOI:10.1016/j.ejphar.2011.09.158
52. Кучер А.Н., Бабушкина Н.П. Роль генетических и средовых факторов в детерминации ответа на метформин. Сахарный диабет. 2021;24(6):571-82 [Kucher АN, Babushkina NP. Role of Genetic and Environmental Factors in Determining the Response to Metformin. Diabetes mellitus. 2021;24(6):571-82 (in Russian)]. DOI:10.14341/DM12744
53. Franks PW, Jablonski KA, Delahanty L, et al. The Pro12Ala variant at the peroxisome proliferator-activated receptor gamma gene and change in obesity-related traits in the Diabetes Prevention Program. Diabetologia. 2007;50(12):2451-60. DOI:10.1007/s00125-007-0826-6

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1. Global report on diabetes. Geneva: World Health Organization, 2018. License: CC BY-NC-SA (in Russian).
2. Park KS. The search for genetic risk factors of type 2 diabetes mellitus. Diabetes Metab J. 2011;35(1):12-22. DOI:10.4093/dmj.2011.35.1.12
3. Moore AF, Jablonski KA, McAteer JB, et al. Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program. Diabetes. 2008;57(9):2503-10. DOI:10.2337/db08-0284
4. Zhou K, Donnelly LA, Kimber CH, et al. Reduced-function SLC22A1 polymorphisms encoding organic cation transporter 1 and glycemic response to metformin: a GoDARTS study. Diabetes. 2009;58(6):1434-9. DOI:10.2337/db08-0896
5. Standards of specialized diabetes care. Eds II Dedov, MV Shestakova, AYu Mayorov. 10th edition. Diabetes mellitus. 2021;24(S1):221 (in Russian). DOI:10.14341/DM12802
6. Meirhaeghe A, Tanck MWT, Fajas L, et al. Study of a new PPARGamma2 promoter polymorphism and haplotype analysis in a French population. Mol Genet Metab. 2005,85(2):140-8. DOI:10.1016/j.ymgme.2005.02.004
7. Montagner A, Rando G, Degueurce G, et al. New insights into the role of PPARs. Prostaglandins Leukot Essent Fatty Acids. 2011;85(5):235-43. DOI:10.1016/j.plefa.2011.04.016
8. Yen CJ, Beamer BA, Negri C, et al. Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun. 1997;18;241(2):270-4. DOI:10.1006/bbrc.1997.7798
9. Frederiksen L, Brødbaek K, Fenger M, et al. Comment: studies of the Pro12Ala polymorphism of the PPAR-gamma gene in the Danish MONICA cohort: homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome. J Clin Endocrinol Metab. 2002;87(8):3989-92. DOI:10.1210/jcem.87.8.8732
10. Sarhangi N, Sharifi F, Hashemian L, et al. PPARG (Pro12Ala) genetic variant and risk of T2DM: a systematic review and meta-analysis. Sci Rep. 2020;10(1):12764. DOI:10.1038/s41598-020-69363-7
11. Wang X, Liu J, Ouyang Y, et al. The association between the Pro12Ala variant in the PPARγ2 gene and type 2 diabetes mellitus and obesity in a Chinese population. PLoS One. 2013;8(8):e71985. DOI:10.1371/journal.pone.0071985
12. Tan GD, Neville MJ, Liverani E, et al. The in vivo effects of the Pro12Ala PPARGamma2 polymorphism on adipose tissue NEFA metabolism: the first use of the Oxford Biobank. Diabetologia. 2006;49(1):158-68. DOI:10.1007/s00125-005-0044-z
13. Ho JS, Germer S, Tam CH, et al. Association of the PPARG Pro12Ala polymorphism with type 2 diabetes and incident coronary heart disease in a Hong Kong Chinese population. Diabetes Res Clin Pract. 2012;97(3):483-91. DOI:10.1016/j.diabres.2012.03.012
14. Biryukova EV. Molekulyarno-geneticheskie, gormonal'no-metabolicheskie i klinicheskie aspekty metabolicheskogo sindroma. Avtoref. dis. … kand. med. nauk. Moscow. 2009 (in Russian).
15. Mkrtumyan AM, Biryukova EV, Markina NV. Molekulyarno-geneticheskie osobennosti, kharakter metabolizma glyukozy i funktsiya endoteliya u bol'nykh metabolicheskim sindromom russkoy populyatsii. Diabetes mellitus. 2008;11(4):26-30 (in Russian). DOI:10.14341/2072-0351-5585
16. Chistiakov DA, Potapov VA, Khodirev DS, et al. The PPARGamma Pro12Ala variant is associated with insulin sensitivity in Russian normoglycaemic and type 2 diabetic subjects. Diab Vasc Dis Res. 2010;7(1):56-62. DOI:10.1177/1479164109347689
17. Bystrova AA, Ulitina AS, Kim MV, et al. Genetic Risk Factors of Macrovascular Complications in Patients with Type 2 Diabetes. Kardiologiia. 2017;57(2):17-22.
18. Potapov VA. Poisk geneticheskikh markerov, opredelyayushchikh predraspolozhennost' k sakharnomu diabetu tipa 2. Avtoref. dis. … kand. med. nauk. Moscow. 2010 (in Russian).
19. Chernobrivtsev PA, Pishchulina SV, Kishenya MS. Osobennosti raspredeleniya genotipov i allelei Rs1801282 gena PPARG u bol'nykh metabolicheskim sindromom v donetskom regione. Universitetskaya Klinika. 2017;3(24):56-60 (in Russian).
20. Mori H, Ikegami H, Kawaguchi Y, et al. The Pro12 -->Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes. Diabetes. 2001;50(4):891-4. DOI:10.2337/diabetes.50.4.891
21. Galbete C, Toledo E, Martínez-González MA, et al. Pro12Ala variant of the PPARG2 gene increases body mass index: An updated meta-analysis encompassing 49,092 subjects. Obesity (Silver Spring). 2013;21(7):1486-95. DOI:10.1002/oby.20150
22. González Sánchez JL, Serrano Ríos M, Fernández Perez C, et al. Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene on adiposity, insulin sensitivity and lipid profile in the Spanish population. Eur J Endocrinol. 2002;147(4):495-501. DOI:10.1530/eje.0.1470495
23. Bhatt SP, Misra A, Sharma M, et al. Ala/Ala genotype of Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-γ2 gene is associated with obesity and insulin resistance in Asian Indians. Diabetes Technol Ther. 2012;14(9):828-34. DOI:10.1089/dia.2011.0277
24. Cole SA, Mitchell BD, Hsueh WC, et al. The Pro12Ala variant of peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with measures of obesity in Mexican Americans. Int J Obes Relat Metab Disord. 2000;24(4):522-4. DOI:10.1038/sj.ijo.0801210
25. Mansoori A, Amini M, Kolahdooz F, Seyedrezazadeh E. Obesity and Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor-Gamma Gene in Healthy Adults: A Systematic Review and Meta-Analysis. Ann Nutr Metab. 2015;67(2):104-18. DOI:10.1159/000439285
26. Tellechea ML, Aranguren F, Pérez MS, et al. Pro12Ala polymorphism of the peroxisome proliferatoractivated receptor-gamma gene is associated with metabolic syndrome and surrogate measures of insulin resistance in healthy men: interaction with smoking status. Circ J. 2009;73(11):2118-24. DOI:10.1253/circj.cj-09-0320
27. Radha V, Vimaleswaran KS, Babu HN, et al. Role of genetic polymorphism peroxisome proliferator-activated receptor-gamma2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: Evidence for heterogeneity. Diabetes Care. 2006;29(5):1046-51. DOI:10.2337/diacare.2951046
28. Hegele RA, Cao H, Harris SB, et al. Peroxisome proliferator-activated receptor-gamma2 P12A and type 2 diabetes in Canadian Oji-Cree. J Clin Endocrinol Metab. 2000;85(5):2014-9. DOI:10.1210/jcem.85.5.6610
29. Kilpeläinen TO, Lakka TA, Laaksonen DE, et al. SNPs in PPARG associate with type 2 diabetes and interact with physical activity. Med Sci Sports Exerc. 2008;40(1):25-33. 
DOI:10.1249/mss.0b013e318159d1cd
30. Lindi VI, Uusitupa MI, Lindstrom J, et al. Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study. Diabetes. 2002;51(8):2581-6.
31. Valeeva FV, Medvedeva MS, Khasanova KB, et al. Association of gene polymorphisms with body weight changes in prediabetic patients. Mol Biol Rep. 2022.
DOI:10.1007/s11033-022-07254-y
32. Isakova ZhT, Talaibekova ET, Zhyrgalbekova BZh, et al. Gene-gene interaction and the contribution of polymorphic loci of KCNJ11, ADIPOQ, omentin, leptin, TCF7L2 and PPARG genes in the development of type 2 diabetes mellitus in the Kyrgyz population: a case-control genetic association study using MDR-analysis. Problems of Endocrinology. 2018;64(4):216-25 (in Russian). DOI:10.14341/probl8344
33. Hashemian L, Sarhangi N, Afshari M, et al. The role of the PPARG (Pro12Ala) common genetic variant on type 2 diabetes mellitus risk. J Diabetes Metab Disord. 2021;20(2):1385-90. DOI:10.1007/s40200-021-00872-6
34. Al-Naemi AH, Ahmad AJ. Is the rs1801282 (G/C) Polymorphism of PPAR – Gamma Gene Associated with T2DM in Iraqi People? Open Access Maced J Med Sci. 2018;6(3):447-55. DOI:10.3889/oamjms.2018.156
35. Wang F, Han XY, Ren Q, et al. Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population. Chin Med J (Engl). 2009;122(20):2477-82.
36. Meigs JB, Manning AK, Fox CS, et al. Genome-wide association with diabetes-related traits in the Framingham Heart Study. BMC Med Genet. 2007;8 Suppl 1(Suppl 1):S16. DOI:10.1186/1471-2350-8-S1-S16
37. Montagnana M, Fava C, Nilsson PM, et al. The Pro12Ala polymorphism of the PPARG gene is not associated with the metabolic syndrome in an urban population of middle-aged Swedish individuals. Diabet Med. 2008;25(8):902-8. DOI:10.1111/j.1464-5491.2008.02510.x
38. Pattanayak AK, Bankura B, Balmiki N, et al. Role of peroxisome proliferator-activated receptor gamma gene polymorphisms in type 2 diabetes mellitus patients of West Bengal, India. J Diabetes Investig. 2014;5(2):188-91. DOI:10.1111/jdi.12130
39. Hotta K, Kitamoto A, Kitamoto T, et al. Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography. J Hum Genet. 2012;57(5):305-10. DOI:10.1038/jhg.2012.21
40. Oh EY, Min KM, Chung JH, et al. Significance of Pro12Ala Mutation in Peroxisome Proliferator-Activated Receptor-γ2 in Korean Diabetic and Obese Subjects. J Clin Endocrinol Metab. 2000,85(5):1801-4. DOI:10.1210/jcem.85.5.6499
41. Bakhashab S, Filimban N, Altall RM, et al. The Effect Sizes of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants on Type 2 Diabetes Mellitus Risk among the Western Saudi Population: A Cross-Sectional Prospective Study. Genes (Basel). 2020;11(1):98. DOI:10.3390/genes11010098
42. Kruzliak P, Haley AP, Starcevic JN, et al. Polymorphisms of the peroxisome proliferator-activated receptor-γ (rs1801282) and its coactivator-1 (rs8192673) are associated with obesity indexes in subjects with type 2 diabetes mellitus. Cardiovasc Diabetol. 2015;14:42. DOI:10.1186/s12933-015-0197-0 
43. Sikhayeva N, Iskakova A, Saigi-Morgui N, et al. Association between 28 single nucleotide polymorphisms and type 2 diabetes mellitus in the Kazakh population: a case-control study. BMC Med Genet. 2017;18(1):76. DOI:10.1186/s12881-017-0443-2
44. Ben Ali S, Ben Yahia F, Sediri Y, et al. Gender-specific effect of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma-2 gene on obesity risk and leptin levels in a Tunisian population. Clin Biochem. 2009;42(16-17):1642-7. DOI:10.1016/j.clinbiochem.2009.08.019
45. Phani NM, Vohra M, Rajesh S, et al. Implications of critical PPARγ2, ADIPOQ and FTO gene polymorphisms in type 2 diabetes and obesity-mediated susceptibility to type 2 diabetes in an Indian population. Mol Genet Genomics. 2016;291(1):193-204. DOI:10.1007/s00438-015-1097-4
46. Vinnik NI, Kutsenko LA, Kutsenko NL, et al. Osobennosti klinicheskoi effektivnosti primeneniya pioglitazona v kompleksnoi terapii bol'nykh s ishemicheskoi bolezn'yu serdtsa na fone metabolicheskogo sindroma. Arterial'naya gipertenziya. 2011;1(15):79-86 (in Russian).
47. Kawaguchi-Suzuki M, Frye RF. Current clinical evidence on pioglitazone pharmacogenomics. Front Pharmacol. 2013;4:147. DOI:10.3389/fphar.2013.00147
48. Hsieh MC, Lin KD, Tien KJ, et al. Common polymorphisms of the peroxisome proliferator-activated receptor-gamma (Pro12Ala) and peroxisome proliferator-activated receptor-gamma coactivator-1 (Gly482Ser) and the response to pioglitazone in Chinese patients with type 2 diabetes mellitus. Metabolism. 2010;59(8):1139-44. DOI:10.1016/j.metabol.2009.10.030
49. Eremenko TV, Matsievskiy NA, Vorokhobina NV, et al. Clinical effect of thiazolidinediones in subjects with disorders of carbohydrate metabolism in case of polymorphism rs1801282. Obesity and metabolism. 2020;17(2):193-9 (in Russian). DOI:10.14341/omet9943
50. Blüher M, Lübben G, Paschke R. Analysis of the relationship between the Pro12Ala variant in the PPAR-gamma2 gene and the response rate to therapy with pioglitazone in patients with type 2 diabetes. Diabetes Care. 2003;26(3):825-31. DOI:10.2337/diacare.26.3.825
51. Namvaran F, Azarpira N, Rahimi-Moghaddam P, Dabbaghmanesh MH. Polymorphism of peroxisome proliferator-activated receptor γ (PPARγ) Pro12Ala in the Iranian population: relation with insulin resistance and response to treatment with pioglitazone in type 2 diabetes. Eur J Pharmacol. 2011;671(1-3):1-6. DOI:10.1016/j.ejphar.2011.09.158
52. Kucher АN, Babushkina NP. Role of Genetic and Environmental Factors in Determining the Response to Metformin. Diabetes mellitus. 2021;24(6):571-82 (in Russian). DOI:10.14341/DM12744
53. Franks PW, Jablonski KA, Delahanty L, et al. The Pro12Ala variant at the peroxisome proliferator-activated receptor gamma gene and change in obesity-related traits in the Diabetes Prevention Program. Diabetologia. 2007;50(12):2451-60. DOI:10.1007/s00125-007-0826-6

К.Б. Хасанова*, М.С. Медведева, Е.В. Валеева, Ж.А. Родыгина, Т.А. Киселева, Ф.В. Валеева

ФГБОУ ВО «Казанский государственный медицинский университет» Минздрава России, Казань, Россия
*kamilya_khasanova@mail.ru

________________________________________________

Kamilya B. Khasanova*, Maria S. Medvedeva, Elena V. Valeeva, Zhanna A. Rodygina, Tatiana A. Kiseleva, Farida V. Valeeva

Kazan State Medical University, Kazan, Russia
*kamilya_khasanova@mail.ru