Альманах клинической медицины. 2019; 47: 112-119
Ассоциации ожирения с обеспеченностью витамином D в зависимости от полиморфизмов rs2228570 гена VDR и rs9939609 гена FTO у жителей средней полосы и Крайнего Севера России
https://doi.org/10.18786/2072-0505-2019-47-015Аннотация
Актуальность. Показано, что обеспеченность витамином D зависит от величины индекса массы тела (ИМТ). Вклад в развитие дефицита витамина D вносят генетические полиморфизмы.
Цель – изучить обеспеченность витамином D населения разных регионов Российской Федерации в зависимости от величины ИМТ и полиморфизмов rs2228570 гена VDR и rs9939609 гена FTO.
Материал и методы. Идентификация полиморфизмов rs2228570 гена VDR и rs9939609 гена FTO проведена у 311 человек (136 проживали в средней полосе России, 175 – на Крайнем Севере). Концентрацию в сыворотке крови 25-гидроксивитамина D (25(ОН)D) определяли иммуноферментным методом в осенне-зимний период. Генотипирование проводили с применением аллель-специфичной амплификации с детекцией результатов в режиме реального времени с использованием TaqMan-зондов, комплементарных полиморфным участкам ДНК, и амплификатора CFX96 Real Time System (“Bio-Rad”, США). Изучали полиморфизмы rs9939609 гена связи с жировой массой и ожирением (FTO), местоположение 16q12.2, а также rs2228570 гена рецептора витамина D (VDR), местоположение 12q13.11.
Результаты. Выраженный дефицит витамина D (уровень 25(ОН)D в сыворотке крови <20 нг/мл) отмечался у 39,7% (54/136) населения средней полосы России, у 40% (14/35) пришлых и у 30,7% (43/140) коренных жителей Крайнего Севера (ненцы). При ожирении у жителей средней полосы России уровень 25(ОН)D в сыворотке крови был ниже, а у коренного населения Крайнего Севера – выше, чем при ИМТ<30 (р<0,05). У коренного населения северного региона выявлена статистически значимая связь аллеля С полиморфизма rs2228570 гена VDR (отношение шансов (ОШ) 2,5, 95% доверительный интервал (ДИ) [1,46–4,27], p=0,0006) и генотипа АА полиморфизма rs9939609 гена FTO (ОШ 8,83, 95% ДИ [0,94–82,5], p=0,02) с дефицитом витамина D.
Заключение. Ассоциация между ожирением и обеспеченностью витамином D у людей с полиморфизмами rs2228570 гена VDR и rs9939609 гена FTO зависит от их этнической принадлежности.
Список литературы
1. Kılıç S, Sılan F, Hız MM, Işık S, Ögretmen Z, Özdemir Ö. Vitamin D receptor gene BSMI, FOKI, APAI, and TAQI polymorphisms and the risk of atopic dermatitis. J Investig Allergol Clin Immunol. 2016;26(2):106–10. doi: 10.18176/jiaci.0020.
2. Gilbert R, Bonilla C, Metcalfe C, Lewis S, Evans DM, Fraser WD, Kemp JP, Donovan JL, Hamdy FC, Neal DE, Lane JA, Smith GD, Lathrop M, Martin RM. Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer: a nested case-control study. Cancer Causes Control. 2015;26(2):205–18. doi: 10.1007/s10552-014-0500-5.
3. Hossein-Nezhad A, Eshaghi SM, Maghbooli Z, Mirzaei K, Shirzad M, Curletto B, Chen TC. The role of vitamin D deficiency and vitamin D receptor genotypes on the degree of collateralization in patients with suspected coronary artery disease. Biomed Res Int. 2014;2014:304250. doi: 10.1155/2014/304250.
4. Jakubowska-Pietkiewicz E, Młynarski W, Klich I, Fendler W, Chlebna-Sokół D. Vitamin D receptor gene variability as a factor influencing bone mineral density in pediatric patients. Mol Biol Rep. 2012;39(5):6243–50. doi: 10.1007/s11033-012-1444-z.
5. Wang G, Zhang Q, Xu N, Xu K, Wang J, He W, Yang T. Associations between two polymorphisms (FokI and BsmI) of vitamin D receptor gene and type 1 diabetes mellitus in Asian population: a meta-analysis. PLoS One. 2014;9(3):e89325. doi: 10.1371/journal.pone.0089325.
6. Каронова ТЛ, Гринева ЕН, Михеева ЕП, Беляева ОД, Красильникова ЕИ, Никитина ИЛ. Уровень витамина D и его взаимосвязь с количеством жировой ткани и содержанием адипоцитокинов у женщин репродуктивного возраста. Проблемы эндокринологии. 2012;58(6):19–23.
7. Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Hiraki LT, Cooper JD, Dastani Z, Li R, Houston DK, Wood AR, Michaëlsson K, Vandenput L, Zgaga L, Yerges-Armstrong LM, McCarthy MI, Dupuis J, Kaakinen M, Kleber ME, Jameson K, Arden N, Raitakari O, Viikari J, Lohman KK, Ferrucci L, Melhus H, Ingelsson E, Byberg L, Lind L, Lorentzon M, Salomaa V, Campbell H, Dunlop M, Mitchell BD, Herzig KH, Pouta A, Hartikainen AL; Genetic Investigation of Anthropometric Traits-GIANT Consortium, Streeten EA, Theodoratou E, Jula A, Wareham NJ, Ohlsson C, Frayling TM, Kritchevsky SB, Spector TD, Richards JB, Lehtimäki T, Ouwehand WH, Kraft P, Cooper C, März W, Power C, Loos RJ, Wang TJ, Järvelin MR, Whittaker JC, Hingorani AD, Hyppönen E. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 2013;10(2):e1001383. doi: 10.1371/journal.pmed.1001383.
8. Turer CB, Lin H, Flores G. Prevalence of vitamin D deficiency among overweight and obese US children. Pediatrics. 2013;131(1):e152–61. doi: 10.1542/peds.2012-1711.
9. Larcombe L, Mookherjee N, Slater J, Slivinski C, Dantouze J, Singer M, Whaley C, Denechezhe L, Matyas S, Decter K, Turner-Brannen E, Ramsey C, Nickerson P, Orr P. Vitamin D, serum 25(OH)D, LL-37 and polymorphisms in a Canadian First Nation population with endemic tuberculosis. Int J Circumpolar Health. 2015;74(1):28952. doi: 10.3402/ijch.v74.28952.
10. Lourenço BH, Qi L, Willett WC, Cardoso MA; ACTION Study Team. FTO genotype, vitamin D status, and weight gain during childhood. Diabetes. 2014;63(2):808–14. doi: 10.2337/db13-1290.
11. Батурин АК, Погожева АВ, Кешабянц ЭЭ, Старовойтов МЛ, Кобелькова ИВ, Камбаров АО. Изучение питания, антропометрических показателей и состава тела у коренного и пришлого населения российской Арктики. Вопросы питания. 2017;86(5):12–8. doi: 10.24411/0042-8833-2017-00070.
12. Козлов АИ, Вершубская ГГ, Негашева МА. Полиморфизм гена рецептора витамина D (VDR) в выборках населения Европейской России и Приуралья. Пермский медицинский журнал. 2016;33(5):60–6. doi: 10.17816/pmj33560-66.
13. Osman E, Al Anouti F, El Ghazali G, Haq A, Mirgani R, Al Safar H. Frequency of rs731236 (Taql), rs2228570 (Fok1) of Vitamin-D Receptor (VDR) gene in Emirati healthy population. Meta Gene. 2015;6:49–52. doi: 10.1016/j.mgene.2015.09.001.
14. Батурин АК, Сорокина ЕЮ, Погожева АВ, Кешабянц ЭЭ, Кобелькова ИВ, Камбаров АО, Елизарова ЕВ, Тутельян ВА. Изучение ассоциации полиморфизмов rs993609 гена FTO и rs659366 гена UCP2 с ожирением у населения Арктической зоны Российской Федерации. Вопросы питания. 2017;86(3):32–9. doi: 10.24411/0042-8833-2017-00042.
15. Harbron J, van der Merwe L, Zaahl MG, Kotze MJ, Senekal M. Fat mass and obesity-associated (FTO) gene polymorphisms are associated with physical activity, food intake, eating behaviors, psychological health, and modeled change in body mass index in overweight/ obese Caucasian adults. Nutrients. 2014;6(8): 3130–52. doi: 10.3390/nu6083130.
Almanac of Clinical Medicine. 2019; 47: 112-119
Associations between obesity and vitamin D availability depending on the rs2228570 polymorphism of the VDR gene and rs9939609 polymorphism of the FTO gene in the midland and the Extreme North of Russia
https://doi.org/10.18786/2072-0505-2019-47-015Abstract
Background: It has been shown that vitamin D availability depends on the body mass index (BMI). Genetic polymorphisms contribute to the development of vitamin D deficiency.
Aim: To study the availability of vitamin D in the population of various regions of the Russian Federation, depending on the BMI values and the rs2228570 polymorphisms of the VDR gene and rs9939609 of the FTO gene.
Materials and methods: The rs2228570 polymorphisms of the VDR gene and rs9939609 of the FTO gene were identified in 311 subjects (136, from the midland of Russia, and 175 from the Far North). Serum 25-hydroxyvitamin D [25(OH)D] levels were measured by an immunoenzyme assay in the autumn and winter seasons. Genotyping was performed with the allele-specific amplification and real-time detection of results using TaqMan probes complementary to the polymorphic DNA segments and the CFX96 Real Time System amplifier (Bio-Rad, USA). We studied associations of the rs9939609 polymorphism of the fat mass and obesity-associated (FTO) gene located at 16q12.2, as well as the rs2228570 polymorphism of the vitamin D receptor gene (VDR) located at 12q13.11.
Results: Frank vitamin D deficiency (serum 25 (OH) D level<20 ng/ml) was observed in 39.7% (54/136) of the sample from the midland, in 40% (14/35) of the migrants and in 30.7% (43/140) of the indigenous inhabitants of the Far North (Nenets). Obese residents of the midland Russia had significantly lower serum 25(OH)D levels, and the indigenous population of the Far North had significantly higher levels than those with BMI<30 (р<0.05). In the indigenous population of the Northern Region, there was a significant association between vitamin D deficiency and C allele of the rs2228570 polymorphism of the VDR gene (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.46–4.27, p=0.0006) and the AA genotype of the rs9939609 polymorphism of the FTO gene (OR 8.83, 95% CI 0.94–82.5, p=0.02).
Conclusion: The association between obesity and vitamin D availability in the individuals with the rs2228570 polymorphism of the VDR gene and the rs9939609 polymorphism of the FTO gene depends on their ethnicity.
References
1. Kılıç S, Sılan F, Hız MM, Işık S, Ögretmen Z, Özdemir Ö. Vitamin D receptor gene BSMI, FOKI, APAI, and TAQI polymorphisms and the risk of atopic dermatitis. J Investig Allergol Clin Immunol. 2016;26(2):106–10. doi: 10.18176/jiaci.0020.
2. Gilbert R, Bonilla C, Metcalfe C, Lewis S, Evans DM, Fraser WD, Kemp JP, Donovan JL, Hamdy FC, Neal DE, Lane JA, Smith GD, Lathrop M, Martin RM. Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer: a nested case-control study. Cancer Causes Control. 2015;26(2):205–18. doi: 10.1007/s10552-014-0500-5.
3. Hossein-Nezhad A, Eshaghi SM, Maghbooli Z, Mirzaei K, Shirzad M, Curletto B, Chen TC. The role of vitamin D deficiency and vitamin D receptor genotypes on the degree of collateralization in patients with suspected coronary artery disease. Biomed Res Int. 2014;2014:304250. doi: 10.1155/2014/304250.
4. Jakubowska-Pietkiewicz E, Młynarski W, Klich I, Fendler W, Chlebna-Sokół D. Vitamin D receptor gene variability as a factor influencing bone mineral density in pediatric patients. Mol Biol Rep. 2012;39(5):6243–50. doi: 10.1007/s11033-012-1444-z.
5. Wang G, Zhang Q, Xu N, Xu K, Wang J, He W, Yang T. Associations between two polymorphisms (FokI and BsmI) of vitamin D receptor gene and type 1 diabetes mellitus in Asian population: a meta-analysis. PLoS One. 2014;9(3):e89325. doi: 10.1371/journal.pone.0089325.
6. Karonova TL, Grineva EN, Mikheeva EP, Belyaeva OD, Krasil'nikova EI, Nikitina IL. Uroven' vitamina D i ego vzaimosvyaz' s kolichestvom zhirovoi tkani i soderzhaniem adipotsitokinov u zhenshchin reproduktivnogo vozrasta. Problemy endokrinologii. 2012;58(6):19–23.
7. Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Hiraki LT, Cooper JD, Dastani Z, Li R, Houston DK, Wood AR, Michaëlsson K, Vandenput L, Zgaga L, Yerges-Armstrong LM, McCarthy MI, Dupuis J, Kaakinen M, Kleber ME, Jameson K, Arden N, Raitakari O, Viikari J, Lohman KK, Ferrucci L, Melhus H, Ingelsson E, Byberg L, Lind L, Lorentzon M, Salomaa V, Campbell H, Dunlop M, Mitchell BD, Herzig KH, Pouta A, Hartikainen AL; Genetic Investigation of Anthropometric Traits-GIANT Consortium, Streeten EA, Theodoratou E, Jula A, Wareham NJ, Ohlsson C, Frayling TM, Kritchevsky SB, Spector TD, Richards JB, Lehtimäki T, Ouwehand WH, Kraft P, Cooper C, März W, Power C, Loos RJ, Wang TJ, Järvelin MR, Whittaker JC, Hingorani AD, Hyppönen E. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 2013;10(2):e1001383. doi: 10.1371/journal.pmed.1001383.
8. Turer CB, Lin H, Flores G. Prevalence of vitamin D deficiency among overweight and obese US children. Pediatrics. 2013;131(1):e152–61. doi: 10.1542/peds.2012-1711.
9. Larcombe L, Mookherjee N, Slater J, Slivinski C, Dantouze J, Singer M, Whaley C, Denechezhe L, Matyas S, Decter K, Turner-Brannen E, Ramsey C, Nickerson P, Orr P. Vitamin D, serum 25(OH)D, LL-37 and polymorphisms in a Canadian First Nation population with endemic tuberculosis. Int J Circumpolar Health. 2015;74(1):28952. doi: 10.3402/ijch.v74.28952.
10. Lourenço BH, Qi L, Willett WC, Cardoso MA; ACTION Study Team. FTO genotype, vitamin D status, and weight gain during childhood. Diabetes. 2014;63(2):808–14. doi: 10.2337/db13-1290.
11. Baturin AK, Pogozheva AV, Keshabyants EE, Starovoitov ML, Kobel'kova IV, Kambarov AO. Izuchenie pitaniya, antropometricheskikh pokazatelei i sostava tela u korennogo i prishlogo naseleniya rossiiskoi Arktiki. Voprosy pitaniya. 2017;86(5):12–8. doi: 10.24411/0042-8833-2017-00070.
12. Kozlov AI, Vershubskaya GG, Negasheva MA. Polimorfizm gena retseptora vitamina D (VDR) v vyborkakh naseleniya Evropeiskoi Rossii i Priural'ya. Permskii meditsinskii zhurnal. 2016;33(5):60–6. doi: 10.17816/pmj33560-66.
13. Osman E, Al Anouti F, El Ghazali G, Haq A, Mirgani R, Al Safar H. Frequency of rs731236 (Taql), rs2228570 (Fok1) of Vitamin-D Receptor (VDR) gene in Emirati healthy population. Meta Gene. 2015;6:49–52. doi: 10.1016/j.mgene.2015.09.001.
14. Baturin AK, Sorokina EYu, Pogozheva AV, Keshabyants EE, Kobel'kova IV, Kambarov AO, Elizarova EV, Tutel'yan VA. Izuchenie assotsiatsii polimorfizmov rs993609 gena FTO i rs659366 gena UCP2 s ozhireniem u naseleniya Arkticheskoi zony Rossiiskoi Federatsii. Voprosy pitaniya. 2017;86(3):32–9. doi: 10.24411/0042-8833-2017-00042.
15. Harbron J, van der Merwe L, Zaahl MG, Kotze MJ, Senekal M. Fat mass and obesity-associated (FTO) gene polymorphisms are associated with physical activity, food intake, eating behaviors, psychological health, and modeled change in body mass index in overweight/ obese Caucasian adults. Nutrients. 2014;6(8): 3130–52. doi: 10.3390/nu6083130.
