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Association between Psoriasis and MTHFR polymorphisms: a systematic review and meta-analysis

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Abstract

Methylenetetrahydrofolate reductase (MTHFR) is key to the metabolism of folic acid, with loss of function mutations resulting in elevated homocysteine levels, a known risk factor for cardiovascular disease. Psoriasis patients may demonstrate hyperhomocysteinemia. To assess for the association between psoriasis and MTHFR C677T and A1298C polymorphisms. A systematic literature search was conducted in MEDLINE, Embase, Cochrane CENTRAL, and Web of Science. Case reports, case–control, cohort, and cross-sectional studies with full-text availability in English were considered. Meta-analysis was conducted with pooled ORs calculated via the random effects model (I2 > 50%). Of 917 records identified, 10 studies were selected for review of 1965 psoriasis patients and 2030 controls. Meta-analysis demonstrated that for MTHFR C677T, there were positive associations between psoriasis and the allele contrast model (C vs T, pooled OR = 1.69, 95% CI = 1.10–2.59), the additive model (CC vs TT, pooled OR = 2.44, 95% CI = 1.06–5.60), the dominant model (CC vs CT + TT, pooled OR = 1.77, 95% CI = 1.06–2.98), and the recessive model (CC + CT vs TT, pooled OR = 2.08, 95% CI = 1.05–4.13). For MTHFR A1298C, there were positive associations between psoriasis and the allele contrast model (A vs C, pooled OR = 3.57, 95% CI = 1.19–10.68), the dominant model (AA vs AC + CC, pooled OR = 4.44, 95% CI = 1.12–17.66), and the overdominant model (AC vs AA + CC, pooled OR = 0.26, 95% CI = 0.07–0.91). There may be a link between the C677T and A1298C polymorphisms with psoriasis diagnosis.

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Data availability

Data and materials supporting the findings in this study are available upon request.

References

  1. Greb JE, Goldminz AM, Elder JT et al (2016) Psoriasis. Nat Rev Dis Primer 2(1):1–17. https://doi.org/10.1038/nrdp.2016.82

    Article  Google Scholar 

  2. Michalek IM, Loring B, John SM (2017) A systematic review of worldwide epidemiology of psoriasis. J Eur Acad Dermatol Venereol 31(2):205–212. https://doi.org/10.1111/jdv.13854

    Article  CAS  PubMed  Google Scholar 

  3. Wu JJ, Feldman SR, Koo J, Marangell LB (2018) Epidemiology of mental health comorbidity in psoriasis. J Dermatol Treat 29(5):487–495. https://doi.org/10.1080/09546634.2017.1395800

    Article  CAS  Google Scholar 

  4. Armstrong AW, Read C (2020) Pathophysiology, clinical presentation, and treatment of psoriasis: a review. JAMA 323(19):1945–1960. https://doi.org/10.1001/jama.2020.4006

    Article  CAS  PubMed  Google Scholar 

  5. Di Cesare A, Di Meglio P, Nestle FO (2009) The IL-23/Th17 axis in the immunopathogenesis of Psoriasis. J Invest Dermatol 129(6):1339–1350. https://doi.org/10.1038/jid.2009.59

    Article  CAS  PubMed  Google Scholar 

  6. Gisondi P, Bellinato F, Girolomoni G, Albanesi C (2020) Pathogenesis of chronic plaque psoriasis and its intersection with cardio-metabolic comorbidities. Front Pharmacol 11:117. https://doi.org/10.3389/fphar.2020.00117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Goyette P, Sumner JS, Milos R et al (1994) Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nat Genet 7(2):195–200. https://doi.org/10.1038/ng0694-195

    Article  CAS  PubMed  Google Scholar 

  8. Hoffman M (2011) Hypothesis: hyperhomocysteinemia is an indicator of oxidant stress. Med Hypotheses 77(6):1088–1093. https://doi.org/10.1016/j.mehy.2011.09.009

    Article  CAS  PubMed  Google Scholar 

  9. Al Mutairi F (2020) Hyperhomocysteinemia: clinical insights. J Cent Nerv Syst Dis 12:1179573520962230. https://doi.org/10.1177/1179573520962230

    Article  PubMed  PubMed Central  Google Scholar 

  10. Clément A, Amar E, Brami C et al (2022) MTHFR SNPs (methyl tetrahydrofolate reductase, single nucleotide polymorphisms) C677T and A1298C prevalence and serum homocysteine levels in >2100 hypofertile caucasian male patients. Biomolecules 12(8):1086. https://doi.org/10.3390/biom12081086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Moll S, Varga EA (2015) Homocysteine and MTHFR mutations. Circulation 132(1):e6–e9. https://doi.org/10.1161/CIRCULATIONAHA.114.013311

    Article  CAS  PubMed  Google Scholar 

  12. Yakub M, Moti N, Parveen S, Chaudhry B, Azam I, Iqbal MP (2012) Polymorphisms in MTHFR, MS and CBS genes and homocysteine levels in a Pakistani population. PLoS ONE 7(3):e33222. https://doi.org/10.1371/journal.pone.0033222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Barker SD, Bale S, Booker J et al (2009) Development and characterization of reference materials for MTHFR, SERPINA1, RET, BRCA1, and BRCA2 genetic testing. J Mol Diagn 11(6):553–561. https://doi.org/10.2353/jmoldx.2009.090078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ulvik A, Ueland PM, Fredriksen A et al (2007) Functional inference of the methylenetetrahydrofolate reductase 677C > T and 1298A > C polymorphisms from a large-scale epidemiological study. Hum Genet 121(1):57–64. https://doi.org/10.1007/s00439-006-0290-2

    Article  CAS  PubMed  Google Scholar 

  15. Razi B, Imani D, Hassanzadeh Makoui M, Rezaei R, Aslani S (2020) Association between MTHFR gene polymorphism and susceptibility to autism spectrum disorders: systematic review and meta-analysis. Res Autism Spectr Disord 70:101473. https://doi.org/10.1016/j.rasd.2019.101473

    Article  Google Scholar 

  16. Ota K, Takahashi T, Han A, Damvaeba S, Mizunuma H, Kwak-Kim J (2020) Effects of MTHFR C677T polymorphism on vitamin D, homocysteine and natural killer cell cytotoxicity in women with recurrent pregnancy losses. Hum Reprod 35(6):1276–1287. https://doi.org/10.1093/humrep/deaa095

    Article  CAS  PubMed  Google Scholar 

  17. Luo Z, Lu Z, Muhammad I et al (2018) Associations of the MTHFR rs1801133 polymorphism with coronary artery disease and lipid levels: a systematic review and updated meta-analysis. Lipids Health Dis 17(1):191. https://doi.org/10.1186/s12944-018-0837-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhang HZ, Wu JH, Huang Q et al (2021) Associations of methylenetetrahydrofolate reductase gene (MTHFR) rs1801131 and rs1801133 polymorphisms with susceptibility to vitiligo: a meta-analysis. J Cosmet Dermatol 20(7):2359–2368. https://doi.org/10.1111/jocd.13857

    Article  PubMed  Google Scholar 

  19. Petrone I, Bernardo PS, dos Santos EC, Abdelhay E (2021) MTHFR C677T and A1298C polymorphisms in breast cancer, gliomas and gastric cancer: a review. Genes 12(4):587. https://doi.org/10.3390/genes12040587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dong X, Wang J, Wang G, Wang J, Wang L, Du Y (2021) MTHFR A1298C gene polymorphism on stroke risk: an updated meta-analysis. Genes Environ 43(1):40. https://doi.org/10.1186/s41021-021-00208-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tobin AM, Hughes R, Hand EB, Leong T, Graham IM, Kirby B (2011) Homocysteine status and cardiovascular risk factors in patients with psoriasis: a case–control study. Clin Exp Dermatol 36(1):19–23. https://doi.org/10.1111/j.1365-2230.2010.03877.x

    Article  PubMed  Google Scholar 

  22. Ganguly P, Alam SF (2015) Role of homocysteine in the development of cardiovascular disease. Nutr J 14(1):6. https://doi.org/10.1186/1475-2891-14-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Baiqiu W, Songbin F, Guiyin Z, Pu L (2000) Study of the relationship between psoriasis and the polymorphic site C677T of methylenetetrahydrofolate reductase. Chin Med Sci J Chung-Kuo Hsueh Ko Hsueh Tsa Chih 15(2):119–120

    CAS  Google Scholar 

  24. Sibani S, Christensen B, O’Ferrall E et al (2000) Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria. Hum Mutat 15(3):280–287. https://doi.org/10.1002/(SICI)1098-1004(200003)15:3%3c280::AID-HUMU9%3e3.0.CO;2-I

    Article  CAS  PubMed  Google Scholar 

  25. Agha Z, Shaiq PA, Ahmed S et al (2018) A study of ACE, eNOS and MTHFR association with psoriasis in Pakistani population. Meta Gene 15:65–69. https://doi.org/10.1016/j.mgene.2017.12.001

    Article  Google Scholar 

  26. Asefi M, Vaisi-Raygani A, Khodarahmi R et al (2014) Methylentetrahydrofolatereductase (rs1801133) polymorphism and psoriasis: contribution to oxidative stress, lipid peroxidation and correlation with vascular adhesion protein 1, preliminary report. J Eur Acad Dermatol Venereol JEADV 28(9):1192–1198. https://doi.org/10.1111/jdv.12262

    Article  CAS  PubMed  Google Scholar 

  27. Huraib GB, Harthi FA, Arfin M, Khlaiwi AA, Rizvi S, Al-Asmari A (2019) Methylenetetrahydrofolate reductase C677T gene polymorphism as risk factor for psoriasis in Saudis. Biomark Insights 14:1177271919830973. https://doi.org/10.1177/1177271919830973

    Article  PubMed  PubMed Central  Google Scholar 

  28. Izmirli M, Sen BB, Rifaioglu E et al (2016) Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in psoriasis in southern Turkey. An Bras Dermatol 91(5):611–613. https://doi.org/10.1590/abd1806-4841.20164766

    Article  PubMed  PubMed Central  Google Scholar 

  29. Kilic S, Ozdemir O, Silan F et al (2017) Possible association between germline methylenetetrahydrofolate reductase gene polymorphisms and psoriasis risk in a Turkish population. Clin Exp Dermatol 42(1):8–13. https://doi.org/10.1111/ced.12909

    Article  CAS  PubMed  Google Scholar 

  30. Vasku V, Bienertova-Vasku J, Necas M, Vasku A (2009) MTHFR (methylenetetrahydrofolate reductase) C677T polymorphism and psoriasis. Clin Exp Med 9(4):327–331. https://doi.org/10.1007/s10238-009-0054-0

    Article  CAS  PubMed  Google Scholar 

  31. Luo Q, Zeng J, Li W et al (2018) Interaction of MTHFR gene with smoking and alcohol use and haplotype combination susceptibility to psoriasis in Chinese population. Immunol Res 66(4):543–547. https://doi.org/10.1007/s12026-018-9017-4

    Article  CAS  PubMed  Google Scholar 

  32. Liew SC, Das-Gupta E, Wong SF, Lee N, Safdar N, Jamil A (2012) Association of methylentetraydrofolate reductase (MTHFR) 677 C > T gene polymorphism and homocysteine levels in psoriasis vulgaris patients from Malaysia: a case–control study. Nutr J 11:1. https://doi.org/10.1186/1475-2891-11-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Weger W, Hofer A, Stanger O et al (2008) The methylenetetrahydrofolate reductase 677C>T gene polymorphism is not associated with chronic plaque psoriasis. Exp Dermatol 17(9):748–751. https://doi.org/10.1111/j.1600-0625.2008.00713.x

    Article  CAS  PubMed  Google Scholar 

  34. Qi JH, Qi JH, Shi N, Chen YJ, Nie G (2015) Association between MTHFR 677C/T polymorphism and psoriasis risk: a meta-analysis. Genet Mol Res GMR 14(2):3869–3876. https://doi.org/10.4238/2015.April.22.16

    Article  CAS  PubMed  Google Scholar 

  35. Wu D, Shi D, Yang L, Zhu X (2016) Association between methylenetetrahydrofolate reductase C677T polymorphism and psoriasis: a meta-analysis. J Dermatol 43(2):162–169. https://doi.org/10.1111/1346-8138.13039

    Article  CAS  PubMed  Google Scholar 

  36. Page MJ, McKenzie JE, Bossuyt PM et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https://doi.org/10.1136/bmj.n71

    Article  PubMed  PubMed Central  Google Scholar 

  37. Komsa-Penkova R, Dimitrov B, Tonchev P, Gospodinova K, Gospodinov D (2020) Place of mthfr gene polymorphism C677T as a risk factor in obese male patients with psoriasis. Clin Nutr ESPEN 40:431. https://doi.org/10.1016/j.clnesp.2020.09.083

    Article  Google Scholar 

  38. Wells G, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Accessed July 17, 2021. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

  39. Malerba M, Gisondi P, Radaeli A, Sala R, Pinton PGC, Girolomoni G (2006) Plasma homocysteine and folate levels in patients with chronic plaque psoriasis. Br J Dermatol 155(6):1165–1169. https://doi.org/10.1111/j.1365-2133.2006.07503.x

    Article  CAS  PubMed  Google Scholar 

  40. Tsai TY, Yen H, Huang YC (2019) Serum homocysteine, folate and vitamin B12 levels in patients with psoriasis: a systematic review and meta-analysis. Br J Dermatol 180(2):382–389. https://doi.org/10.1111/bjd.17034

    Article  CAS  PubMed  Google Scholar 

  41. Frosst P, Blom HJ, Milos R et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1):111–113. https://doi.org/10.1038/ng0595-111

    Article  CAS  PubMed  Google Scholar 

  42. Weisberg I, Tran P, Christensen B, Sibani S, Rozen R (1998) A Second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 64(3):169–172. https://doi.org/10.1006/mgme.1998.2714

    Article  CAS  PubMed  Google Scholar 

  43. Lin X, Meng X, Song Z (2019) Homocysteine and psoriasis. Biosci Rep 39(11):BSR20190867. https://doi.org/10.1042/BSR20190867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Campalani E, Arenas M, Marinaki AM, Lewis CM, Barker JNWN, Smith CH (2007) Polymorphisms in folate, pyrimidine, and purine metabolism are associated with efficacy and toxicity of methotrexate in psoriasis. J Invest Dermatol 127(8):1860–1867. https://doi.org/10.1038/sj.jid.5700808

    Article  CAS  PubMed  Google Scholar 

  45. Chango A, Emery-Fillon N, de Courcy GP et al (2000) A polymorphism (80G->A) in the reduced folate carrier gene and its associations with folate status and homocysteinemia. Mol Genet Metab 70(4):310–315. https://doi.org/10.1006/mgme.2000.3034

    Article  CAS  PubMed  Google Scholar 

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RM and KH equally contributed in conducting the systematic review, writing the main manuscript text, and preparing figures 1-4 and tables 1-2. WG assisted with the systematic review and mediated resolution of conflicts during the study selection and data extraction process. SN performed statistical analyses for meta-analysis. KL provided assistance in study conception. TK and KS revised the manuscript. All authors reviewed the manuscript.

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Correspondence to Rika Matsuo.

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Matsuo, R., Haught, K., Guo, W. et al. Association between Psoriasis and MTHFR polymorphisms: a systematic review and meta-analysis. Arch Dermatol Res 316, 184 (2024). https://doi.org/10.1007/s00403-024-02905-5

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