The frequency of Raynaud’s phenomenon in patients with methylenetetrahydrofolate reductase gene mutation and hyperhomocysteinemia
The frequency of Raynaud’s phenomenon in patients with methylenetetrahydrofolate reductase gene mutation and hyperhomocysteinemia
Background/aim: Raynaud’s phenomenon (RP) is not a rare health problem; global prevalence is about 3%–20%. Etiology andpathophysiology of this pathology has not been clarified. There are many precipitating factors resulting in RP. Hyperhomocysteinemiaresulting from methylenetetrahydrofolate reductase (MTHFR) gene mutation may have a role in its etiology. The aim of this study was toobserve the frequency of RP in patients with MTFHR gene mutation and hyperhomocysteinemia. Possible relationships among vitaminB12, folic acid, complete blood count (leukocytes and platelets), and c-reactive protein levels and RP were also analyzed.Materials and methods: A total of 388 patients admitted to the internal medicine, hematology, and obstetric clinics of a universityhospital between January 2012 and April 2013 ranging in age from 21 to 83 (mean age 38.16 ± 13.1) were enrolled in the study. Eightyfive (21.9%) of the patients were male and 303 (78.1%) were female. MTHFR gene mutation was analyzed in 388 patients; 52 (13.4%)were homozygous, 275 (70.9%) were heterozygous, and 61 (15.7%) were found to be negative for the MTHFR gene mutation andaccepted as a control group. Vitamin B12, folic acid, complete blood count (leukocytes and platelets), and c-reactive protein levels werealso analyzed.Results: Homocysteine levels were higher in both heterozygous and homozygous groups (P < 0.05). RP was more frequently observedin patients with elevated homocysteine levels (P < 0.05; X2 = 14.51). There was no significant relationship in other parameters studied.Conclusion: RP was more frequently observed in the groups with the MTHFR mutation and hyperhomocysteinemia. Serumhomocysteine levels in patients with RP may be helpful for diagnosis.
___
- 1. Herrick AL. Pathogenesis of Raynaud’s phenomenon.
Rheumatology 2005; 44(5): 587-596. doi: 10.1093/
rheumatology/keh552
- 2. Belch J, Carlizza A, Carpentier PH, Constans J, Khan F et
al. ESVM guidelines – the diagnosis and management of
Raynaud’s phenomenon. Vasa 2017; 46(6): 413-423. doi:
10.1024/0301-1526/a0006611
- 3. Lazzerini PE, Capecchi PL, Bisogno S, Cozzalupi M, Rossi PC
et al. Homocysteine and Raynaud’s phenomenon: A review.
Autoimmunity Reviews 2010; 9(3): 181-187. doi: 10.1016/j.
autrev.2009.08.004
- 4. Zamora MR, O’Brien RF, Rutherford RB, Weil JV. Serum
endothelin-1 concentrations and cold provocation in primary
Raynaud’s phenomenon. Lancet 1990; 336(8724): 1144–1147.
doi: 10.1016/0140-6736(90)92766-B
- 5. Tucker AT, Pearson RM, Cooke ED, Benjamin N. Effect of
nitric-oxide-generating system on microcirculatory blood
flow in skin of patients with severe Raynaud’s syndrome: a
randomised trial. Lancet 1999; 354(9191): 1670-1675. doi:
10.1016/S0140-6736(99)04095-7
- 6. Bunker CB, Terenghi G, Springall DR, Polak JM, Dowd PM.
Deficiency of calcitonin gene-related peptide in Raynaud’s
phenomenon. Lancet 1990; 336(8730): 1530-1533. doi:
10.1016/0140-6736(90)93307-B
- 7. Kallenberg CG, Vellenga E, Wouda AA, The TH. Platelet
activation, fibrinolytic activity and circulating immune
complexes in Raynaud’s phenomenon. The Journal of
Rheumatology 1982; 9(6): 878-884.
- 8. Belch JJ, McLaren M, Anderson J, Lowe GD, Sturrock RD et
al. Increased prostacyclin metabolites and decreased red cell
deformability in patients with systemic sclerosis and Raynaud’s
syndrome. Prostaglandins, Leukotrienes, and Medicine 1985;
18(3): 401-402.
- 9. Goyle KB, Dormandy JA. Abnormal blood viscosity in
Raynaud’s phenomenon. Lancet 1976; 1(7973): 1317-1318.
doi: 10.1016/s0140-6736(76)92651-91
- 10. Maricq HR, Carpentier PH, Weinrich MC, Keil JE, Palesch
Y et al. Geographic variation in the prevalence of Raynaud’s
phenomenon: a 5 region comparison. The Journal of
Rheumatology 1997; 24(5): 879-889.
- 11. Garner R, Kumari R, Lanyon P, Doherty M, Zhang W.
Prevalence, risk factors and associations of primary Raynaud’s
phenomenon: systematic review and meta-analysis of
observational studies. BMJ Open 2015; 5(3): 6389-6390. doi:
10.1136/bmjopen-2014-006389
- 12. Onbaşi K, Sahin I, Onbaşi O, Ustün Y, Koca D. Raynaud’s
phenomenon in a healthy Turkish population. Clinical
Rheumatology 2005; 24(4): 365-369. doi: 10.1007/s10067-004-
1045-x
- 13. Cakir N, Pamuk ON, Dönmez S, Barutçu A, Diril H et al.
Prevalence of Raynaud’s phenomenon in healthy Turkish
medical students and hospital personnel. Rheumatology
International 2008; 29(2): 185-188. doi: 10.1007/s00296-008-
0666-9
- 14. Schwahn B, Rozen R. Polymorphisms in the
methylentetrahydrofolate reductase gene: clinical
consequences. American Journal of Pharmacogenomics 2001;
1: 189-201. doi: 10.2165/00129785-200101030-00004
- 15. Capelli I, Cianciolo G, Gasperoni L, Zappulo F, Tondolo F et al.
Folic acid and vitamin B12 administration in CKD, why not?
Nutrients 2019; 11(2): 165-172. doi: 10.3390/nu11020383
- 16. Cortese C, Motti C. MTHFR gene polymorphism,
homocysteine and cardiovascular disease. Public Health
Nutrition 2001; 4(2): 493-497. doi: 10.1079/phn2001159
- 17. Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ et al. MTHFR
677C-T polymorphism and risk of coronary heart disease.
JAMA 2002; 288: 2023-2031. doi: 10.1001/jama.288.16.2023
- 18. Engbersen AM, Franken DG, Boers GH, Stevens EM, Trijbels
FJ et al. Thermolabile 5,10-methylenetetrahydrofolate
reductase as a cause of mild hyperhomocysteinemia. American
Journal of Human Genetics 1995; 56(1): 142-150.