شناسایی تغییرات تک نوکلئوتیدی در ژن‌های مرتبط با قدرت عضلانی و دیابت تیپ دو در یک ورزشکار نخبه با استفاده از توالی یابی کل اگزوم: یک گزارش موردی

نویسندگان
بهمن ابراهیمی 1
معرفت سیاه کوهیان 1
علی خازنی 1
سجاد انوشیروانی 1
لطفعلی بلبلی 1
فاطمه اسدی 2
1 گروه تربیت بدنی و علوم ورزشی، دانشگاه محقق اردبیلی، اردبیل، ایران
2 گروه ژنتیک، دانشگاه آزاد علوم و تحقیقات فارس، شیراز، ایران
چکیده
مقدمه

ژنتیک، تغذیه و سبک زندگی در ایجاد چاقی و دیابت تیپ 2 با یکدیگر تعامل دارند. از طرفی گزارش­های ضد و نقیضی در مورد تاثیر ورزش­های قدرتی بر سلامت قلب و عروق و فاکتور­های متابولیکی در ورزشکاران سنگین وزن نخبه وجود دارد. هدف از نگارش مقاله حاضر گزارش تغییرات تک نوکلئوتیدی در برخی از ژن­های مرتبط با قدرت عضلانی و دیابت تیپ 2 در یک ورزشکار سنگین وزن نخبه با استفاده از روش توالی‌یابی کل اگزوم بود.

مورد

پس از اخذ رضایت نامه کتبی از یکی از ورزشکاران عضو تیم ملی وزنه‌برداری مردان، 5 سی‌سی خون دریافت شد. پس از استخراج DNA از نمونه خون جهت بررسی ژن­ها از روش توالی‌یابی کل اگزوم استفاده شد.

نتیجه‌گیری

تغییرات تک نوکلئوتیدی در ژن­های KCNJ11(rs5213, rs5215, rs1800467, rs5219) و PCK1(707555) در ژنوم این ورزشکار مشاهده شد. همچنین واریانت­های جدید (230845794A>G و 230845977G>A) در ژن AGT و (61564052A>G و (61573761T>C در ژن ACE مشاهده شد. مطالعات جدید با حجم نمونه بیشتر لازم است تا ارتباط دقیقه این واریانت­ها با قدرت عضلانی و یا دیابت تیپ 2 در ورشکاران قدرتی سنگین وزن نخبه را مشخص سازد.
کلیدواژه‌ها
ژن
ورزش
ورزشکار نخبه
دیابت تیپ 2
عضلات

عنوان مقاله English

Single nucleotide polymorphisms identification in genes associated to muscles strength and type 2 diabetes in an elite athlete using whole exome sequencing: A Case Report

نویسندگان English

Bahman Ebrahimi 1
Marefat Siyahkohiyan 1
Ali Khazani 1
Sajjad Anoshirvani 1
Lotfali Bolboli 1
Fatmeh Asadi 2
1 Mohaghegh Ardabili University
2 2. Department of Molecular Genetics, Science and Research Branch, Islamic Azad University, Fars, Iran
چکیده English

Introduction

Genetics, nutrition and lifestyle interact to cause type 2 diabetes and obesity. On the other hand, there are conflicting reports about the effect of strength training on cardiovascular health and metabolic factors in professional heaviest-weight-class athletes. The aim of this article was to report single nucleotide changes in some genes associated with muscle strength and type 2 diabetes in an elite heaviest-weight-class athlete using the WES method.

Case

After obtaining written consent from one of the athletes in the men's national weightlifting team, 5 cc of blood was received. After DNA extraction from blood sample, the WES method was used to examine the genes.

Conclusion

Single nucleotide changes in KCNJ11 (rs5213, rs5215, rs1800467, rs5219) and PCK1 (707555) genes were observed in the athlete's genome. New variants (230845794A> G and 230845977G> A) were also observed in the AGT gene and (61564052A> G and (61573761T> C) in the ACE gene. New studies with larger sample sizes are needed to determine the exact association of these variants with muscle strength or type 2 diabetes in elite heaviest-weight-class in weightlifters.

کلیدواژه‌ها English

Genes
Exercise
Elite Athletes
Type 2 Diabetes
muscles
1. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nature Reviews Endocrinology. 2018;14(2):88.
2. Polonsky KS, Sturis J, Bell GI. Seminars in Medicine of the Beth Israel Hospital, Boston. Non-insulin-dependent diabetes mellitus-a genetically programmed failure of the beta cell to compensate for insulin resistance. The New England journal of medicine. 1996;334(12):777.
3. Gibbons A. Diabetes Genes Decline Out of Africa. American Association for the Advancement of Science; 2011.
4. Steinthorsdottir V, Thorleifsson G, Sulem P, Helgason H, Grarup N, Sigurdsson A, et al. Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes. Nature genetics. 2014;46(3):294.
5. Habibipour R, Keshavarz Kiasaraei P. The association study of the E23k Kcnj11 variant with progression of type 2 diabetes among obese individuals in a population in the North of Iran. Iranian Journal of Endocrinology and Metabolism. 2011;13(6):673-80.
6. Barroso I. Genetics of type 2 diabetes. Diabetic Medicine. 2005;22(5):517-35.
7. Makhzoom O, Kabalan Y, Faizeh A-Q. Association of KCNJ11 rs5219 gene polymorphism with type 2 diabetes mellitus in a population of Syria: a case-control study. BMC medical genetics. 2019;20(1):1-6.
8. Beale EG, Harvey BJ, Forest C. PCK1 and PCK2 as candidate diabetes and obesity genes. Cell biochemistry and biophysics. 2007;48(2-3):89-95.
9. Dong Y, Zhang H, Wang X, Feng Q, Chen X, Su Q. A Leu184Val polymorphism in PCK1 gene is associated with type 2 diabetes in Eastern Chinese population with BMI< 23 kg/m2. Diabetes research and clinical practice. 2009;83(2):227-32.
10. Rees SD, Britten AC, Bellary S, O'Hare JP, Kumar S, Barnett AH, et al. The promoter polymorphism-232C/G of the PCK1 gene is associated with type 2 diabetes in a UK-resident South Asian population. BMC Medical Genetics. 2009;10(1):83.
11. Willer CJ, Bonnycastle LL, Conneely KN, Duren WL, Jackson AU, Scott LJ, et al. Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes. Diabetes. 2007;56(1):256-64.
12. Clouthier DE, Comerford SA, Hammer RE. Hepatic fibrosis, glomerulosclerosis, and a lipodystrophy-like syndrome in PEPCK-TGF-beta1 transgenic mice. The Journal of clinical investigation. 1997;100(11):2697-713.
13. Runtuwene J, Cheng K-C, Asakawa A, Amitani H, Amitani M, Morinaga A, et al. Rosmarinic acid ameliorates hyperglycemia and insulin sensitivity in diabetic rats, potentially by modulating the expression of PEPCK and GLUT4. Drug design, development and therapy. 2016;10:2193.
14. Li Y, Liu Y, Chen G. Vitamin A status affects the plasma parameters and regulation of hepatic genes in streptozotocin-induced diabetic rats. Biochimie. 2017;137:1-11.
15. Oda H, Okuda Y, Yoshida Y, Kimura N, Kakinuma A. Phenobarbital reduces blood glucose and gluconeogenesis through down-regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression in rats. Biochemical and Biophysical Research Communications. 2015;466(3):306-11.
16. Amanat S, Ghahri S, Dianatinasab A, Fararouei M, Dianatinasab M. Exercise and Type 2 Diabetes. Physical Exercise for Human Health: Springer; 2020. p. 91-105.
17. Praet SF, Van Loon LJ. Optimizing the therapeutic benefits of exercise in type 2 diabetes. Journal of applied physiology. 2007;103(4):1113-20.
18. Eynon N, Nasibulina ES, Banting LK, Cieszczyk P, Maciejewska-Karlowska A, Sawczuk M, et al. The FTO A/T polymorphism and elite athletic performance: a study involving three groups of European athletes. PloS one. 2013;8(4):e60570.
19. Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, Walts B, et al. The human obesity gene map: the 2005 update. Obesity. 2006;14(4):529-644.
20. Eynon N, Hanson ED, Lucia A, Houweling PJ, Garton F, North KN, et al. Genes for elite power and sprint performance: ACTN3 leads the way. Sports medicine. 2013;43(9):803-17.
21. Haghvirdizadeh P, Mohamed Z, Abdullah NA, Haghvirdizadeh P, Haerian MS, Haerian BS. KCNJ11: genetic polymorphisms and risk of diabetes mellitus. Journal of diabetes research. 2015;2015.
22. Phani NM, Guddattu V, Bellampalli R, Seenappa V, Adhikari P, Nagri SK, et al. Population specific impact of genetic variants in KCNJ11 gene to type 2 diabetes: a case-control and meta-analysis study. PLoS One. 2014;9(9):e107021.
23. Liu Z, Zhang Y, Feng Q, Li Y, Wu G, Zuo J, et al. Association analysis of 30 type 2 diabetes candidate genes in Chinese Han population. Zhongguo yi xue ke xue Yuan xue bao Acta Academiae Medicinae Sinicae. 2006;28(2):124-8.
24. Abdelhamid I, Lasram K, Meiloud G, Halim NB, Kefi R, Samb A, et al. E23K variant in KCNJ11 gene is associated with susceptibility to type 2 diabetes in the Mauritanian population. Primary Care Diabetes. 2014;8(2):171-5.
25. Javorsky M, Klimcakova L, Schroner Z, Zidzik J, Babjakova E, Fabianova M, et al. KCNJ11 gene E23K variant and therapeutic response to sulfonylureas. European journal of internal medicine. 2012;23(3):245-9.
26. Lang VY, Fatehi M, Light PE. Pharmacogenomic analysis of ATP-sensitive potassium channels coexpressing the common type 2 diabetes risk variants E23K and S1369A. Pharmacogenetics and genomics. 2012;22(3):206-14.
27. Wang D-d, Chen X, Yang Y, Liu C-x. Association of Kir6. 2 gene rs5219 variation with type 2 diabetes: A meta-analysis of 21,464 individuals. Primary Care Diabetes. 2018;12(4):345-53.
28. Rastegari A, Rabbani M, Sadeghi HM, Imani EF, Hasanzadeh A, Moazen F. Association of KCNJ11 (E23K) gene polymorphism with susceptibility to type 2 diabetes in Iranian patients. Advanced biomedical research. 2015;4.
29. Nielsen E-MD, Hansen L, Carstensen B, Echwald SM, Drivsholm T, Glümer C, et al. The E23K variant of Kir6. 2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes. Diabetes. 2003;52(2):573-7.
30. Villareal DT, Koster JC, Robertson H, Akrouh A, Miyake K, Bell GI, et al. Kir6. 2 variant E23K increases ATP-sensitive K+ channel activity and is associated with impaired insulin release and enhanced insulin sensitivity in adults with normal glucose tolerance. Diabetes. 2009;58(8):1869-78.
31. M‘t Hart L, van Haeften TW, Dekker JM, Bot M, Heine RJ, Maassen JA. Variations in insulin secretion in carriers of the E23K variant in the KIR6. 2 subunit of the ATP-sensitive K+ channel in the β-cell. Diabetes. 2002;51(10):3135-8.
32. Chavali S, Mahajan A, Tabassum R, Dwivedi OP, Chauhan G, Ghosh S, et al. Association of variants in genes involved in pancreatic β-cell development and function with type 2 diabetes in North Indians. Journal of human genetics. 2011;56(10):695-700.
33. Sakamoto Y, Inoue H, Keshavarz P, Miyawaki K, Yamaguchi Y, Moritani M, et al. SNPs in the KCNJ11-ABCC8 gene locus are associated with type 2 diabetes and blood pressure levels in the Japanese population. Journal of human genetics. 2007;52(10):781-93.
34. Florez JC, Burtt N, De Bakker PI, Almgren P, Tuomi T, Holmkvist J, et al. Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region. Diabetes. 2004;53(5):1360-8.
35. Barroso I, Middelberg RP, Harding A-H, Franks PW, Jakes RW, Clayton D, et al. Candidate gene association study in type 2 diabetes indicates a role for genes involved in β-cell function as well as insulin action. PLoS Biol. 2003;1(1):e20.
36. Hu Q, Chen H, Zuo Y, He Q, He X, Simpson S, et al. Role of PCK1 gene on oil tea-induced glucose homeostasis and type 2 diabetes: an animal experiment and a case-control study. Nutrition & metabolism. 2019;16(1):12.
37. Lindbloom-Hawley S, LeCluyse M, Vandersande V, Lushington GH, Schermerhorn T. Cloning and characterization of feline islet glucokinase. BMC veterinary research. 2014;10(1):130.
38. Fu D, Cong X, Ma Y, Cai H, Cai M, Li D, et al. Genetic polymorphism of glucokinase on the risk of type 2 diabetes and impaired glucose regulation: evidence based on 298, 468 subjects. PloS one. 2013;8(2):e55727.
39. Vaxillaire M, Veslot J, Dina C, Proença C, Cauchi S, Charpentier G, et al. Impact of common type 2 diabetes risk polymorphisms in the DESIR prospective study. Diabetes. 2008;57(1):244-54.
40. Rose CS, Ek J, Urhammer SA, Glümer C, Borch-Johnsen K, Jørgensen T, et al. A− 30G> A polymorphism of the β-cell–specific glucokinase promoter associates with hyperglycemia in the general population of whites. Diabetes. 2005;54(10):3026-31.
41. Siddiqui S, Waghdhare S, Gopi S, Bhargava A, Panda M, Radha V, et al. GCK Gene Screening and Association of GCK Variants With Gestational Diabetes in North Indian Population. Clinical Medicine Insights: Endocrinology and Diabetes. 2018;11:1179551418806896.
42. Corvol P, Jeunemaitre X. Molecular genetics of human hypertension: role of angiotensinogen. Endocrine reviews. 1997;18(5):662-77.
43. Gomez-Gallego F, Santiago C, González-Freire M, Yvert T, Muniesa CA, Serratosa L, et al. The C allele of the AGT Met235Thr polymorphism is associated with power sports performance. Applied Physiology, Nutrition, and Metabolism. 2009;34(6):1108-11.
44. Alves GB, Oliveira EM, Alves CR, Rached HR, Mota GF, Pereira AC, et al. Influence of angiotensinogen and angiotensin-converting enzyme polymorphisms on cardiac hypertrophy and improvement on maximal aerobic capacity caused by exercise training. European Journal of Preventive Cardiology. 2009;16(4):487-92.
45. Maciejewska-Skrendo A, Cięszczyk P, Chycki J, Sawczuk M, Smółka W. Genetic markers associated with power athlete status. Journal of human kinetics. 2019;68(1):17-36.
46. Boraita A, de la Rosa A, Heras ME, Ana I, Canda A, Rabadán M, et al. Cardiovascular adaptation, functional capacity, and angiotensin-converting enzyme I/D polymorphism in elite athletes. Revista Española de Cardiología (English Edition). 2010;63(7):810-9.
47. Charbonneau DE, Hanson ED, Ludlow AT, Delmonico MJ, Hurley BF, Roth SM. ACE genotype and the muscle hypertrophic and strength responses to strength training. Medicine and science in sports and exercise. 2008;40(4):677.
48. Zhao B, Moochhala SM, Tham S-y, Lu J, Chia M, Byrne C, et al. Relationship between angiotensin-converting enzyme ID polymorphism and VO2max of Chinese males. Life sciences. 2003;73(20):2625-30.
49. Guo J, Zhang X, Wang L, Guo Y, Xie M. Prevalence of metabolic syndrome and its components among Chinese professional athletes of strength sports with different body weight categories. PLoS One. 2013;8(11):e79758.