The value of the MTHFR polymorphisms in pathogenesis of nontraumatic necrosis of femoral head

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Abstract


Introduction. Among the etiological factors of non-traumatic avascular necrosis of the femoral head are the following: the prolonged use of corticosteroids, alcohol abuse, systemic lupus erythematosus, sickle cell anemia, the Legg – Calve – Perthes disease, ionizing radiation, cytotoxic agents, etc. At the same time necrosis of the femoral head might occur in the absence of the above factors (idiopathic necrosis). The reasons for idiopathic avascular necrosis could be a mechanical obstacle to the flow of blood, thrombotic occlusion of vessels, extravascular compression.

The purpose of this study is to examine the role of C677T gene mutation of the MTHFR gene in the development of non-traumatic avascular necrosis of the femoral head.

Materials and methods. During this study there was a comparative analysis of the frequency of the C677T gene allelic variants conducted in 41 patients with a verified diagnosis of non-traumatic avascular necrosis (main group) and 320 healthy individuals (control group). The survey program included the study of polymorphisms of MTHFR C677T gene by PCR.

Results. Differences in the frequency of occurrence of C allele of C677T gene MTHFR in the heterozygous state in case of non-traumatic avascular necrosis and in its absence were not statistically significant (51.2% against 37.2% respectively, χ2 = 3.014, p = 0.083). The genotype TT (T in the homozygous state) of the C677T MTHFR gene was detected in 19.5% of the main group patients. A similar index in the control group was two times lower and amounted to 9.0 percent, the differences between groups statistically significant, χ2 = 4.314, p = 0.038.

Conclusion. The study showed the importance of having the T C677T MTHFR gene in the pathogenesis of non-traumatic avascular necrosis of the femoral head. The data obtained and the analysis of the current literature suggests that this polymorphism is one of genetic predictors of non-traumatic avascular necrosis of the femoral head and other cardiovascular diseases as well.


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About the authors

Mikhail A. Panin

Peoples Friendship University of Russia

Email: panin-mihail@yandex.ru

Russian Federation, Moscow

MD, associate Professor in the department of traumatology and orthopedics

Nikolai V. Zagorodnii

Peoples Friendship University of Russia

Email: zag@mail.ru

Russian Federation, Moscow

MD, PhD Professor, corresponding member of RAMS, head of traumatology and orthopedics department

Larisa M. Samokhodskaya

Lomonosov Moscow State University

Email: sam@mail.ru

Russian Federation, Moscow

MD, associate Professor, head of Department of laboratory diagnostics

Andrei V. Boiko

Peoples Friendship University of Russia

Author for correspondence.
Email: boiko120393@gmail.com

Russian Federation, Moscow

resident of traumatology and orthopedics department

References

  1. Shannon BD, Trousdale RT. Femoral osteotomies for avascular necrosis of the femoral head. Clin Orthop Relat Res. 2004;(418):34-40. https://doi.org/10.1097/00003086-200401000-00007
  2. DeSmet AA, Dalinka MK, Alazraki NP, Daffner RH, El-Khoury GY, Kneeland JB. Expert Panel on Musculoskeletal Imaging. Diagnostic imaging of avascular necrosis of the hip. Reston, VA: American College of Radiology (ACR); 2005.
  3. Mont MA, Marulanda GA, Jones LC, Saleh KJ, Gordon N, Hungerford DS, Steinberg ME. Systematic analysis of classification systems for osteonecrosis of the femoral head. J Bone Joint Surg Am. 2006;88(Suppl 3):16-26. https://doi.org/10.2106/JBJS.F.00457
  4. Ikeuchi K, Hasegawa Y, Seki T, Takegami Y, Amano T, Ishiguro N. Epidemiology of nontraumatic osteonecrosis of the femoral head in Japan. Mod Rheumatol. 2015;25(2):278-281. https://doi.org/10.3109/14397595.2014.932038
  5. Панин М.А., Загородний Н.В., Карчебный Н.Н., Садков И.А., Петросян А.С., Закирова А.Р. Современный взгляд на патогенез нетравматического остеонекроза. Вестник травматологии и ортопедии имени Н.Н. Приорова. 2017;(2):69-75. [Panin MA, Zagorodny NV, Karchebny NN, Sadkov IA, Petrosyan AS, Zakirova AR. Modern view to the pathogenesis of non-traumatic osteonecrosis. Vestnik travmatologii i ortopedii imeni N.N. Priorova. 2017;(2):69-75. (In Russ.).]
  6. Jones LC, Mont MA, Le TB, Petri M, Hungerford DS, Wang P, Glueck CJ. Procoagulants and osteonecrosis. J Rheumatol. 2003;30(4):783-791.
  7. Glueck CJ, Freiberg RA, Oghene J, Fontaine RN, Wang P. Association between the T-786C eNOS polymorphism and idiopathic osteonecrosis of the head of the femur. J Bone Joint Surg Am. 2007;89(11):2460-2466. https://doi.org/10.2106/JBJS.F.01421
  8. Jiang S, Li J, Zhang Y, Venners SA, Tang G, Wang Y, Li Z, Xu X, Wang B, Huo Y. Methylenetetrahydrofolate reductase C677T polymorphism, hypertension and risk of stroke: a prospective, nested case-control study. Int J Neurosci. 2017;127(3):253-260. https://doi.org/10.1080/00207454.2016.1183126
  9. Mao X, Han L. The relationship of methylenetetrahydrofolate reductase gene C677T polymorphism and ischemic stroke in Chinese Han population. Ann Clin Lab Sci. 2018;48(2):242-247.
  10. Arina CA, Amir D, Siregar Y, Sembiring RJ. The role of polymorphism gen methylene tetra hydrofolate reductase (MTHFR) C677T in ischaemic stroke patients with and without hypertension. Open Access Maced J Med Sci. 2019;7(1):29-32. https://doi.org/10.3889/oamjms.2019.026
  11. Trifonova EA, Swarovskaya MG, Ganzha OA, Voronkova OV, Gabidulina TV, Stepanov VA. The interaction effect of angiogenesis and endothelial dysfunction-related gene variants increases the susceptibility of recurrent pregnancy loss. J Assist Reprod Genet. 2019;36(4):717-726. https://doi.org/10.1007/s10815-019-01403-2
  12. Wolski H, Kurzawinska G, Drews K, Barlik M, Kadziolka P, Malewski Z, Mikolajska-Ptas P, Bylewski M, Seremak-Mrozikiewicz A. MTHFR genetic polymorphism and the risk of intrauterine fetal death in Polish women. Ginekol Pol. 2019;90(2):76-81. https://doi.org/10.5603/GP.2019.0013
  13. Zhang L, Chen B. Correlation between MTHFR polymorphisms and glaucoma: a meta-analysis. Mol Genet Genomic Med. 2019;7(4):e00538. https://doi.org/10.1002/mgg3.538
  14. Xu WH, Zhuang Y, Han X, Yuan ZL. Methylenetetrahydrofolate reductase C677T polymorphism and diabetic retinopathy risk: a meta-analysis of the Chinese population. J Int Med Res. 2020;48(1):300060518816834. https://doi.org/10.1177/0300060518816834
  15. Narayanan A, Khanchandani P, Borkar RM, Ambati CR, Roy A, Han X, Bhoskar RN, Ragampeta S, Gannon F, Mysorekar V, Karanam B, V SM, Sivaramakrishnan V. Avascular necrosis of femoral head: a metabolomic, biophysical, biochemical, electron microscopic and histopathological characterization. Sci Rep. 2017;7(1):10721. https://doi.org/10.1038/s41598-017-10817-w
  16. Андреенко Е.Ю., Самоходская Л.М., Балацкий А.В., Макаревич П.И., Бойцов С.А. Прогностическая значимость носительства аллельных вариантов генов, контролирующих систему гемостаза, и их сочетания с традиционными факторами риска в раннем развитии ишемической болезни сердца. Кардиоваскулярная терапия и профилактика. 2011;(8):32–39. [Andreenko EY, Samokhotskaya LM, Balatsky AV, Makarevich PI, Boytsov SA. The prognostic value of allele polymorphisms genes determining hemostasis and their combinations with known risk factors in ischemic cardiac disease development. Kardiovaskularnaya terapia i profilaktika. 2011;(8):32-39. (In Russ.).]
  17. Kutlar A, Kutlar F, Turker I, Tural C. The methylene tetrahydrofolate reductase (C677T) mutation as a potential risk factor for avascular necrosis in sickle cell disease. Hemoglobin. 2001;25(2):213-217. https://doi.org/10.1081/hem-100104029
  18. Hou J, Zeng X, Xie Y, Wu H, Zhao P. Genetic polymorphisms of methylenetetrahydrofolate reductase C677T and risk of ischemic stroke in a southern Chinese Hakka population. Medicine (Baltimore). 2018;97(51):e13645. https://doi.org/10.1097/MD.0000000000013645
  19. Пономаренко И.В., Сукманова И.А. Традиционные факторы риска и генные мутации тромбоза, ассоциированные с острым коронарным синдромом у пациентов молодого возраста. Кардиология. 2019;59(1S):19-24. [Ponomarenko IV, Sukmanova IA. Thrombosis risk factors and gene mutations in young age patients with acute coronary syndrome. Kardiologiia. 2019;59(1S):19-24. (In Russ.).] https://doi.org/10.18087/cardio.2602

Supplementary files

Supplementary Files Action
1.
Fig. 1. Frequency of the C677T gene allelic variants in patients with non-traumatic avascular necrosis in the main and control groups

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2.
Fig. 2. Family history of patients with non-traumatic avascular necrosis in the presence and absence of a homozygous variant of TT gene C677T MTHFR

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Copyright (c) 2020 Panin M.A., Zagorodnii N.V., Samokhodskaya L.M., Boiko A.V.

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