Hostname: page-component-cb9f654ff-p5m67 Total loading time: 0 Render date: 2025-08-12T09:03:36.127Z Has data issue: false hasContentIssue false

Serum folate levels and the risk of psoriasis: evidence from observational study and Mendelian randomisation

Published online by Cambridge University Press:  10 April 2025

Chang-Jie Du
Affiliation:
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China
Jian-Wen Ye
Affiliation:
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China
Yuan-Chen Zhao
Affiliation:
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China
Dong-Sheng Di*
Affiliation:
Department of Health Promotion and Behavioral Sciences, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China Teaching Center for Preventive Medicine, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China
Rui-Xue Leng*
Affiliation:
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui, People’s Republic of China
*
Corresponding author: Rui-Xue Leng; Email: lengruixue@ahmu.edu.cn, Dong-Sheng Di; Email: didongsheng@ahmu.edu.cn
Corresponding author: Rui-Xue Leng; Email: lengruixue@ahmu.edu.cn, Dong-Sheng Di; Email: didongsheng@ahmu.edu.cn

Abstract

This study aimed to investigate the relationship between serum folate levels and the risk of psoriasis by integrating observational study with Mendelian Randomisation (MR) analysis. We firstly conducted an observational study using data from the National Health and Nutrition Examination Survey (NHANES). Subsequently, genetic instruments were selected for two-sample MR analyses to investigate the causal relationship between serum folate levels and the risk of psoriasis. The observational study showed no significant association between serum folate levels and psoriasis. In the fully adjusted model, neither serum folate level as a continuous variable (OR = 0·99, 95 % CI: 0·98, 1·00, P = 0·071) nor serum folate quartiles Q4 compared to Q1 (OR = 0·83, 95 % CI: 0·58, 1·19, P = 0·309) showed statistical significance. The MR analysis revealed that higher genetically predicted serum folate levels from Icelandic and Danish populations were significantly associated with a reduced risk of psoriasis (OR = 0·63, 95 % CI: 0·45, 0·88, P = 0·005). Similarly, higher genetically predicted serum folate levels from South Asian populations were significantly associated with a lower risk of psoriasis (OR = 0·84, 95 % CI: 0·72, 0·98, P = 0·025). Integrating observational study with MR analysis suggests that serum folate levels are protective factors against psoriasis, indicating that higher serum folate levels may help prevent the onset of the disease.

Information

Type
Research Article
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of The Nutrition Society

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

Footnotes

Chang-Jie Du, Jian-Wen Ye, Yuan-Chen Zhao contributed equally.

References

Greb, JE, Goldminz, AM, Elder, JT, et al. (2016) Psoriasis. Nat Rev Dis Primers 2, 16082.CrossRefGoogle ScholarPubMed
Armstrong, AW & Read, C (2020) Pathophysiology, clinical presentation, and treatment of psoriasis: a review. JAMA 323, 19451960.CrossRefGoogle ScholarPubMed
Griffiths, CE & Barker, JN (2007) Pathogenesis and clinical features of psoriasis. Lancet (London, England) 370, 263271.CrossRefGoogle ScholarPubMed
Christophers, E (2001) Psoriasis--epidemiology and clinical spectrum. Clin Exp Dermatol 26, 314320.CrossRefGoogle ScholarPubMed
Miller, IM, Ellervik, C, Yazdanyar, S, et al. (2013) Meta-analysis of psoriasis, cardiovascular disease, and associated risk factors. J Am Acad Dermatol 69, 10141024.CrossRefGoogle ScholarPubMed
Lyon, P, Strippoli, V, Fang, B, et al. (2020) B Vitamins and one-carbon metabolism: implications in human health and disease. Nutrients 12, 2867.CrossRefGoogle ScholarPubMed
Coates, LC, Merola, JF, Grieb, SM, et al. (2020) Methotrexate in psoriasis and psoriatic arthritis. J Rheumatol Supplement 96, 3135.CrossRefGoogle ScholarPubMed
Lopez-Olivo, MA, Siddhanamatha, HR, Shea, B, et al. (2014) Methotrexate for treating rheumatoid arthritis. Cochrane Database Syst Rev 2014, issue 6, CD000957.CrossRefGoogle Scholar
Mazaud, C & Fardet, L (2017) Relative risk of and determinants for adverse events of methotrexate prescribed at a low dose: a systematic review and meta-analysis of randomized placebo-controlled trials. Br J Dermatol 177, 978986.CrossRefGoogle Scholar
Baran, W, Batycka-Baran, A, Zychowska, M, et al. (2014) Folate supplementation reduces the side effects of methotrexate therapy for psoriasis. Expert Opin Drug Saf 13, 10151021.CrossRefGoogle ScholarPubMed
Al-Dabagh, A, Davis, SA, Kinney, MA, et al. (2013) The effect of folate supplementation on methotrexate efficacy and toxicity in psoriasis patients and folic acid use by dermatologists in the USA. Am J Clin Dermatol 14, 155161.CrossRefGoogle ScholarPubMed
Malerba, M, Gisondi, P, Radaeli, A, et al. (2006) Plasma homocysteine and folate levels in patients with chronic plaque psoriasis. Br J Dermatol 155, 11651169.CrossRefGoogle ScholarPubMed
Fry, L, Macdonald, A, Almeyda, J, et al. (1971) The mechanism of folate deficiency in psoriasis. Br J Dermatol 84, 539544.CrossRefGoogle ScholarPubMed
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, 748751.CrossRefGoogle Scholar
Liew, SC, Das-Gupta, E, Wong, SF, et al. (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.CrossRefGoogle Scholar
Cakmak, SK, Gül, U, Kiliç, C, et al. (2009) Homocysteine, vitamin B12 and folic acid levels in psoriasis patients. J Eur Academy Dermatol Venereol: JEADV 23, 300303.CrossRefGoogle ScholarPubMed
Lambie, DG & Johnson, RH (1985) Drugs and folate metabolism. Drugs 30, 145155.CrossRefGoogle ScholarPubMed
Tsai, TY, Yen, H & Huang, YC (2019) Serum homocysteine, folate and vitamin B(12) levels in patients with psoriasis: a systematic review and meta-analysis. Br J Dermatol 180, 382389.CrossRefGoogle ScholarPubMed
Emdin, CA, Khera, AV & Kathiresan, S (2017) Mendelian randomization. JAMA 318, 19251926.CrossRefGoogle ScholarPubMed
Sheehan, NA, Didelez, V, Burton, PR, et al. (2008) Mendelian randomisation and causal inference in observational epidemiology. PLoS Med 5, e177.CrossRefGoogle ScholarPubMed
Liu, Y, Geng, T, Wan, Z, et al. (2022) Associations of serum folate and vitamin B12 levels with cardiovascular disease mortality among patients with type 2 diabetes. JAMA Netw Open 5, e2146124.CrossRefGoogle ScholarPubMed
Ma, R, Cui, L, Cai, J, et al. (2024) Association between systemic immune inflammation index, systemic inflammation response index and adult psoriasis: evidence from NHANES. Front Immunol 15, 1323174.CrossRefGoogle ScholarPubMed
Johnson, CL, Paulose-Ram, R, Ogden, CL, et al. (2013) National health and nutrition examination survey: analytic guidelines, 1999–2010. Vital Health Statistics Ser 2, Data Evaluation Methods Res 124.Google ScholarPubMed
Grarup, N, Sulem, P, Sandholt, CH, et al. (2013) Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets. PLos Genet 9, e1003530.CrossRefGoogle ScholarPubMed
Palmer, TM, Lawlor, DA, Harbord, RM, et al. (2012) Using multiple genetic variants as instrumental variables for modifiable risk factors. Stat Methods Med Res 21, 223242.CrossRefGoogle ScholarPubMed
Jacobs, BM, Stow, D, Hodgson, S, et al. (2024) Genetic architecture of routinely acquired blood tests in a British South Asian cohort. Nat Commun 15, 8929.CrossRefGoogle Scholar
Stuart, PE, Tsoi, LC, Nair, RP, et al. (2022) Transethnic analysis of psoriasis susceptibility in South Asians and Europeans enhances fine-mapping in the MHC and genomewide. HGG Adv 3, 100069.Google ScholarPubMed
Burgess, S, Foley, CN & Zuber, V (2018) Inferring causal relationships between risk factors and outcomes from genome-wide association study data. Ann Rev Genomics Hum Genet 19, 303327.CrossRefGoogle ScholarPubMed
Hemani, G, Bowden, J & Davey Smith, G (2018) Evaluating the potential role of pleiotropy in Mendelian randomization studies. Hum Mol Genet 27, R195R208.CrossRefGoogle ScholarPubMed
Bowden, J, Davey Smith, G & Burgess, S (2015) Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol 44, 512525.CrossRefGoogle ScholarPubMed
Bowden, J, Davey Smith, G, Haycock, PC, et al. (2016) Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol 40, 304314.CrossRefGoogle ScholarPubMed
Zhu, Z, Zhang, F, Hu, H, et al. (2016) Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nat Genet 48, 481487.CrossRefGoogle ScholarPubMed
Hemani, G, Zheng, J, Elsworth, B, et al. (2018) The MR-Base platform supports systematic causal inference across the human phenome. eLife 7, e34408.CrossRefGoogle ScholarPubMed
Refsum, H, Helland, S & Ueland, PM (1989) Fasting plasma homocysteine as a sensitive parameter of antifolate effect: a study of psoriasis patients receiving low-dose methotrexate treatment. Clin Pharmacol Therapeutics 46, 510520.CrossRefGoogle ScholarPubMed
Vanizor Kural, B, Orem, A, Cimşit, G, et al. (2003) Plasma homocysteine and its relationships with atherothrombotic markers in psoriatic patients. Clin Chim Acta; Int J Clin Chem 332, 2330.CrossRefGoogle ScholarPubMed
Karabudak, O, Ulusoy, RE, Erikci, AA, et al. (2008) Inflammation and hypercoagulable state in adult psoriatic men. Acta Dermato-Venereologica 88, 337340.CrossRefGoogle ScholarPubMed
Gisondi, P, Malerba, M, Malara, G, et al. (2010) C-reactive protein and markers for thrombophilia in patients with chronic plaque psoriasis. Int J Immunopathol Pharmacol 23, 11951202.CrossRefGoogle ScholarPubMed
Sharaf, ESFA, Ghanem, BM, Marzouk, HF, et al. (2022) Serum homocysteine, folic acid and vitamin B12 levels in patients with psoriasis vulgaris. Egypt J Hosp Med 88, 33043309.CrossRefGoogle Scholar
Juzeniene, A, Stokke, KT, Thune, P, et al. (2010) Pilot study of folate status in healthy volunteers and in patients with psoriasis before and after UV exposure. J Photochem Photobiol, B 101, 111116.CrossRefGoogle ScholarPubMed
Yang, H, Song, J, Li, A, et al. (2023) Genetically predicted levels of folate, vitamin B(12), and risk of autoimmune diseases: a Mendelian randomization study. Front Immunol 14, 1139799.CrossRefGoogle ScholarPubMed
Crider, KS, Yang, TP, Berry, RJ, et al. (2012) Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate’s role. Adv Nutr (Bethesda, Md) 3, 2138.CrossRefGoogle ScholarPubMed
Ly, A, Hoyt, L, Crowell, J, et al. (2012) Folate and DNA methylation. Antioxid Redox Signaling 17, 302326.CrossRefGoogle ScholarPubMed
Choi, SW & Mason, JB (2000) Folate and carcinogenesis: an integrated scheme. J Nutr 130, 129132.CrossRefGoogle ScholarPubMed
Wu, CH, Huang, TC & Lin, BF (2017) Folate deficiency affects dendritic cell function and subsequent T helper cell differentiation. J Nutr Biochem 41, 6572.CrossRefGoogle ScholarPubMed
Garbicz, J, Całyniuk, B, Górski, M, et al. (2021) Nutritional therapy in persons suffering from psoriasis. Nutrients 14, 119.CrossRefGoogle ScholarPubMed
Supplementary material: File

Du et al. supplementary material

Du et al. supplementary material
Download Du et al. supplementary material(File)
File 689 KB