Login Register Cart 0
Generic placeholder image

Current Rheumatology Reviews

Editor-in-Chief

ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Genetic Association of VDR gene Apa1 and Taq1 Variants with Scleroderma in an Iranian Northeast Population

Author(s): Seyedeh Zahra Mirfeizi, Majid Nabizadeh-Marvast, Mohammad-Hassan Jokar, Houshang Rafatpanah, Kamila Hashemzadeh and Hassan Mehrad-Majd*

Volume 19, Issue 1, 2023

Published on: 27 July, 2022

Page: [49 - 57] Pages: 9

DOI: 10.2174/2772432817666220530110524

Price: $65

Abstract

Background: Despite vigorous research efforts, the etiology of scleroderma (systemic sclerosis (SSc)) remains still unclear and both genetic and environmental factors clearly contribute to the pathogenesis of scleroderma. Reports of aberrant vitamin D status in scleroderma patients suggest a need for considering the genotype and allele frequencies of VDR gene polymorphisms. This case-control study aimed to investigate the possible association of two common polymorphisms of the VDR gene (ApaI, and TaqI) with susceptibility to scleroderma in an Iranian population.

Methods: Using polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP), ApaI and TaqI polymorphisms in the VDR region were genotyped in 51 patients with scleroderma and 50 healthy controls. Logistic regression analysis was performed to calculate the genotypes odds ratios (ORs) as a measure of association with the presence of scleroderma. Haplotype and linkage disequilibrium analyses were also performed on the detected genotypes.

Results: No significant differences were found for the allelic and genotype distributions of ApaI and TaqI polymorphisms between patients with scleroderma and healthy controls (p>0.05). In haplotype analysis, three haplotypes TA, CA, and TC, with a frequency greater than 1% were identified. However, none of them was associated with the risk of scleroderma.

Conclusion: Our preliminary study showed no evidence of an association between ApaI and TaqI polymorphisms and scleroderma. As the association between VDR polymorphisms and autoimmune diseases varies across the different ethnic populations, further large cohort studies are necessary to confirm the results.

Keywords: Scleroderma, systemic sclerosis, vitamin D receptor, VDR, polymorphism, homeostasis.

« Previous Next »
Graphical Abstract

[1]
Sinha R, Smith JC Jr, Soares JH Jr. Calcium and vitamin D in bone metabolism: Analyses of their effects with a short-term in vivo bone model in rats. J Nutr 1988; 118(1): 99-106.
[http://dx.doi.org/10.1093/jn/118.1.99] [PMID: 3335945]
[2]
Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 2002; 110(2): 229-38.
[http://dx.doi.org/10.1172/JCI0215219] [PMID: 12122115]
[3]
Campos RM, Masquio DC, Corgosinho FC, et al. Low vitamin D intake is associated with increase in cardiovascular risk factors in obese adolescents. Endocr Regul 2015; 49(1): 11-9.
[http://dx.doi.org/10.4149/endo_2015_01_11] [PMID: 25687676]
[4]
Boyle BJ, Zhao XY, Cohen P, Feldman D. Insulin-like growth factor binding protein-3 mediates 1 alpha,25-dihydroxyvitamin d(3) growth inhibition in the LNCaP prostate cancer cell line through p21/WAF1. J Urol 2001; 165(4): 1319-24.
[http://dx.doi.org/10.1016/S0022-5347(01)69892-6] [PMID: 11257709]
[5]
Derakhshanian H, Javanbakht MH, Zarei M, Djalali E, Djalali M. Vitamin D increases IGF-I and insulin levels in experimental diabetic rats. Growth Horm IGF Res 2017; 36: 57-9.
[6]
Ali TM, El Esawy B, Elaskary A. Effect of paricalcitol on pancreatic oxidative stress, inflammatory markers, and glycemic status in diabetic rats. Ir J Med Sci 2018; 187(1): 75-84.
[http://dx.doi.org/10.1007/s11845-017-1635-7] [PMID: 28551720]
[7]
Fang F, Ni K, Cai Y, Shang J, Zhang X, Xiong C. Effect of vitamin D supplementation on polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials. Complement Ther Clin Pract 2017; 26: 53-60.
[http://dx.doi.org/10.1016/j.ctcp.2016.11.008] [PMID: 28107851]
[8]
Dixon BM, Barker T, McKinnon T, et al. Positive correlation between circulating cathelicidin antimicrobial peptide (hCAP18/LL-37) and 25-hydroxyvitamin D levels in healthy adults. BMC Res Notes 2012; 5(1): 575.
[http://dx.doi.org/10.1186/1756-0500-5-575] [PMID: 23095332]
[9]
Kempker JA, Martin GS. Vitamin D and sepsis: From associations to causal connections. Inflamm Allergy Drug Targets 2013; 12(4): 246-52.
[http://dx.doi.org/10.2174/18715281113129990048] [PMID: 23782212]
[10]
Wang QM, Luo X, Studzinski GP. Cyclin-dependent kinase 6 is the principal target of p27/Kip1 regulation of the G1-phase traverse in 1,25-dihydroxyvitamin D3-treated HL60 cells. Cancer Res 1997; 57(14): 2851-5.
[PMID: 9230188]
[11]
Jiang H, Lin J, Su ZZ, Collart FR, Huberman E, Fisher PB. Induction of differentiation in human promyelocytic HL-60 leukemia cells activates p21, WAF1/CIP1, expression in the absence of p53. Oncogene 1994; 9(11): 3397-406.
[PMID: 7936668]
[12]
Moffatt KA, Johannes WU, Hedlund TE, Miller GJ. Growth inhibitory effects of 1alpha, 25-dihydroxyvitamin D(3) are mediated by increased levels of p21 in the prostatic carcinoma cell line ALVA-31. Cancer Res 2001; 61(19): 7122-9.
[PMID: 11585744]
[13]
Shahin D, El-Farahaty RM, Houssen ME, et al. Serum 25-OH vitamin D level in treatment-naïve systemic lupus erythematosus patients: Relation to disease activity, IL-23 and IL-17. Lupus 2017; 26(9): 917-26.
[http://dx.doi.org/10.1177/0961203316682095] [PMID: 27927883]
[14]
Gao CC, Liu SY, Wu ZZ, et al. Severe vitamin D deficiency increases the risk for moderate to severe disease activity in Chinese patients with SLE. Lupus 2016; 25(11): 1224-9.
[http://dx.doi.org/10.1177/0961203316635289] [PMID: 26921268]
[15]
Lima GL, Paupitz J, Aikawa NE, et al. Vitamin d supplementation in adolescents and young adults with juvenile systemic lupus erythematosus for improvement in disease activity and fatigue scores: a randomized, double-blind, placebo-controlled trial. Arthritis Care Res (Hoboken) 2016; 68(1): 91-8.
[http://dx.doi.org/10.1002/acr.22621] [PMID: 25988278]
[16]
Abou-Raya A, Abou-Raya S, Helmii M. The effect of vitamin D supplementation on inflammatory and hemostatic markers and disease activity in patients with systemic lupus erythematosus: A randomized placebo-controlled trial. J Rheumatol 2013; 40(3): 265-72.
[http://dx.doi.org/10.3899/jrheum.111594] [PMID: 23204220]
[17]
Jeffery LE, Raza K, Hewison M. Vitamin D in rheumatoid arthritis-towards clinical application. Nat Rev Rheumatol 2016; 12(4): 201-10.
[http://dx.doi.org/10.1038/nrrheum.2015.140] [PMID: 26481434]
[18]
Welsh P, Peters MJL, McInnes IB, et al. Vitamin D deficiency is common in patients with RA and linked to disease activity, but circulating levels are unaffected by TNFα blockade: Results from a prospective cohort study. Ann Rheum Dis 2011; 70(6): 1165-7.
[http://dx.doi.org/10.1136/ard.2010.137265] [PMID: 21047908]
[19]
Vacca A, Cormier C, Mathieu A, Kahan A, Allanore Y. Vitamin D levels and potential impact in systemic sclerosis. Clin Exp Rheumatol 2011; 29(6): 1024-31.
[PMID: 22011638]
[20]
Giuggioli D, Colaci M, Cassone G, et al. Serum 25-OH vitamin D levels in systemic sclerosis: Analysis of 140 patients and review of the literature. Clin Rheumatol 2017; 36(3): 583-90.
[http://dx.doi.org/10.1007/s10067-016-3535-z] [PMID: 28070764]
[21]
Rios Fernández R, Fernández Roldán C, Callejas Rubio JL, Ortego Centeno N. Vitamin D deficiency in a cohort of patients with systemic scleroderma from the south of Spain. J Rheumatol 2010; 37(6): 1355.
[http://dx.doi.org/10.3899/jrheum.091143] [PMID: 20516041]
[22]
Gambichler T, Chrobok I, Höxtermann S, Kreuter A. Significantly decreased serum 25-hydroxyvitamin d levels in a large german systemic sclerosis cohort. J Rheumatol 2011; 38(11): 2492-3.
[http://dx.doi.org/10.3899/jrheum.110695] [PMID: 22045936]
[23]
Zhang L, Duan Y, Zhang TP, et al. Association between the serum level of vitamin D and systemic sclerosis in a Chinese population: A case control study. Int J Rheum Dis 2017; 20(8): 1002-8.
[http://dx.doi.org/10.1111/1756-185X.12794] [PMID: 26619796]
[24]
An L, Sun MH, Chen F, Li JR. Vitamin D levels in systemic sclerosis patients: A meta-analysis. Drug Des Devel Ther 2017; 11: 3119-25.
[http://dx.doi.org/10.2147/DDDT.S144860] [PMID: 29138534]
[25]
Groseanu L, Bojinca V, Gudu T, et al. Low vitamin D status in systemic sclerosis and the impact on disease phenotype. Eur J Rheumatol 2016; 3(2): 50-5.
[http://dx.doi.org/10.5152/eurjrheum.2015.0065] [PMID: 27708971]
[26]
Atteritano M, Santoro D, Corallo G, et al. Skin involvement and pulmonary hypertension are associated with vitamin D insufficiency in scleroderma. Int J Mol Sci 2016; 17(12): 2103.
[http://dx.doi.org/10.3390/ijms17122103] [PMID: 27983651]
[27]
Trombetta AC, Smith V, Gotelli E, et al. Vitamin D deficiency and clinical correlations in systemic sclerosis patients: A retrospective analysis for possible future developments. PLoS One 2017; 12(6): e0179062.
[http://dx.doi.org/10.1371/journal.pone.0179062] [PMID: 28598975]
[28]
Humbert P, Dupond JL, Agache P, et al. Treatment of scleroderma with oral 1,25-dihydroxyvitamin D3: Evaluation of skin involvement using non-invasive techniques. Results of an open prospective trial. Acta Derm Venereol 1993; 73(6): 449-51.
[PMID: 7906461]
[29]
Kato S. The function of vitamin D receptor in vitamin D action. J Biochem 2000; 127(5): 717-22.
[http://dx.doi.org/10.1093/oxfordjournals.jbchem.a022662] [PMID: 10788778]
[30]
Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, et al. The nuclear vitamin D receptor: Biological and molecular regulatory properties revealed. J Bone Mineral Res 1998; 13: 325-49.
[http://dx.doi.org/10.1359/jbmr.1998.13.3.325]
[31]
Bouillon R, Carmeliet G, Verlinden L, et al. Vitamin D and human health: Lessons from vitamin D receptor null mice. Endocr Rev 2008; 29(6): 726-76.
[http://dx.doi.org/10.1210/er.2008-0004] [PMID: 18694980]
[32]
Brumbaugh PF, Haussler MR. 1 Alpha,25-dihydroxycholecalci-] ferol receptors in intestine. I. Association of 1 alpha,25-dihydroxycholecalciferol with intestinal mucosa chromatin. J Biol Chem 1974; 249(4): 1251-7.
[http://dx.doi.org/10.1016/S0021-9258(19)42968-2] [PMID: 4360685]
[33]
McCullough ML, Bostick RM, Mayo TL. Vitamin D gene pathway polymorphisms and risk of colorectal, breast, and prostate cancer. Annu Rev Nutr 2009; 29(1): 111-32.
[http://dx.doi.org/10.1146/annurev-nutr-080508-141248] [PMID: 19400699]
[34]
Rai V, Abdo J, Agrawal S, Agrawal DK, Vitamin D. Vitamin D receptor polymorphism and cancer: An update. Anticancer Res 2017; 37(8): 3991-4003.
[PMID: 28739681]
[35]
Smolders J, Menheere P, Kessels A, Damoiseaux J, Hupperts R. Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis. Mult Scler 2008; 14(9): 1220-4.
[http://dx.doi.org/10.1177/1352458508094399] [PMID: 18653736]
[36]
Speer G, Cseh K, Winkler G, et al. Vitamin D and estrogen receptor gene polymorphisms in type 2 diabetes mellitus and in android type obesity. Eur J Endocrinol 2001; 144(4): 385-9.
[http://dx.doi.org/10.1530/eje.0.1440385] [PMID: 11275948]
[37]
Mahto H, Tripathy R, Das BK, Panda AK. Association between vitamin D receptor polymorphisms and systemic lupus erythematosus in an Indian cohort. Int J Rheum Dis 2018; 21: 468-76.
[http://dx.doi.org/10.1111/1756-185X.13245]
[38]
Kamal A, Gamal SM, Elgengehy FT, Alkemary AK, Siam I. Association of VDR ApaI and TaqI Gene Polymorphisms with the Risk of Scleroderma and Behçet’s Disease. Immunol Invest 2016; 45(6): 531-42.
[http://dx.doi.org/10.1080/08820139.2016.1180302] [PMID: 27409400]
[39]
Masi AT. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the american rheumatism association diagnostic and therapeutic criteria committee. Arthritis Rheum 1980; 23(5): 581-90.
[http://dx.doi.org/10.1002/art.1780230510] [PMID: 7378088]
[40]
Gaunt TR, Rodríguez S, Day IN. Cubic exact solutions for the estimation of pairwise haplotype frequencies: Implications for linkage disequilibrium analyses and a web tool ‘CubeX’. BMC Bioinformatics 2007; 8(1): 428.
[http://dx.doi.org/10.1186/1471-2105-8-428] [PMID: 17980034]
[41]
Li J, Chen S-Y, Liu H-H, et al. Associations of vitamin D receptor single nucleotide polymorphisms with susceptibility to systemic sclerosis. Arch Med Res 2019; 50(6): 368-76.
[http://dx.doi.org/10.1016/j.arcmed.2019.09.006] [PMID: 31678895]
[42]
Kolahi S, Khabbazi A, Khodadadi H, et al. Vitamin D receptor gene polymorphisms in Iranian Azary patients with Behçet’s disease. Scand J Rheumatol 2015; 44(2): 163-7.
[http://dx.doi.org/10.3109/03009742.2014.945477] [PMID: 25421258]
[43]
Mirfeizi Z, Tabaei S, Ravanshad Y, Hashemzadeh K, Kharazmi E, Mehrad-Majd H. Associations between vitamin D receptor polymorphisms and susceptibility to Behcet’s disease: A meta-analysis. Immunol Invest 2018; 47(4): 389-402.
[http://dx.doi.org/10.1080/08820139.2018.1430827] [PMID: 29388852]
[44]
Sweeney C, Curtin K, Murtaugh MA, Caan BJ, Potter JD, Slattery ML. Haplotype analysis of common vitamin D receptor variants and colon and rectal cancers. Cancer Epidemiol Biomarkers Prev 2006; 15(4): 744-9.
[http://dx.doi.org/10.1158/1055-9965.EPI-05-0814] [PMID: 16614118]
[45]
Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Gene 2004; 338(2): 143-56.
[http://dx.doi.org/10.1016/j.gene.2004.05.014] [PMID: 15315818]
[46]
Karray EF, Ben Dhifallah I, Ben Abdelghani K, et al. Associations of vitamin D receptor gene polymorphisms FokI and BsmI with susceptibility to rheumatoid arthritis and Behçet’s disease in Tunisians. Joint Bone Spine 2012; 79(2): 144-8.
[http://dx.doi.org/10.1016/j.jbspin.2011.06.003] [PMID: 21820934]

Rights & Permissions Print Cite
Article Metrics
1
© 2024 Bentham Science Publishers | Privacy Policy