Lack of association of vitamin D receptor gene 3′-haplotypes with psoriasis in Croatian patients
Ivana RUCEVIC
Department of Dermatovenereology, Osijek University Hospital
Private Dermatology Practice
Search for more papers by this authorMario STEFANIC
Clinical Institute of Nuclear Medicine and Radiation Protection, Osijek University Hospital, Osijek, Croatia
Search for more papers by this authorStana TOKIC
Clinical Institute of Nuclear Medicine and Radiation Protection, Osijek University Hospital, Osijek, Croatia
Search for more papers by this authorMelita VUKSIC
Department of Dermatovenereology, Osijek University Hospital
Search for more papers by this authorLjubica GLAVAS-OBROVAC
Clinical Institute of Nuclear Medicine and Radiation Protection, Osijek University Hospital, Osijek, Croatia
Search for more papers by this authorIvana RUCEVIC
Department of Dermatovenereology, Osijek University Hospital
Private Dermatology Practice
Search for more papers by this authorMario STEFANIC
Clinical Institute of Nuclear Medicine and Radiation Protection, Osijek University Hospital, Osijek, Croatia
Search for more papers by this authorStana TOKIC
Clinical Institute of Nuclear Medicine and Radiation Protection, Osijek University Hospital, Osijek, Croatia
Search for more papers by this authorMelita VUKSIC
Department of Dermatovenereology, Osijek University Hospital
Search for more papers by this authorLjubica GLAVAS-OBROVAC
Clinical Institute of Nuclear Medicine and Radiation Protection, Osijek University Hospital, Osijek, Croatia
Search for more papers by this authorAbstract
Cis-acting regulatory variants in biologically relevant pathways and target tissues are a common source of phenotypic variations and individual disease susceptibility. In the skin, vitamin D receptor (VDR) is a master regulator of epidermal barrier function, inflammation, stem cell proliferation and microbial defense; therefore, we tested whether VDR 3′-regulatory haplotypes, a portion of which affect VDR transcriptional efficiency, allelic symmetry and mRNA turnover, were associated with psoriasis vulgaris. For this purpose, three VDR tag polymorphisms that capture most of the variability of the VDR 3′-regulatory element (rs1544410, rs7975232 and rs731236) were genotyped by the polymerase chain reaction restriction fragment length polymorphism method in 180 Caucasian patients with chronic plaque psoriasis and 366 ethnically matched, healthy controls of the Croatian origin. We found no evidence of association for any of the selected polymorphisms. Similarly, none of the 3′-VDR restriction haplotypes were associated with the risk for development of psoriasis in Croatian patients. These results show that neither VDR 3′-restriction polymorphisms nor common 3′-regulatory haplotypes contribute to psoriasis risk in the Croatian population.
References
- 1 Schön MP, Boehncke WH. Psoriasis. N Engl J Med 2005; 352: 1899–1912.
- 2 Tanghetti EA. The role of topical vitamin D modulators in psoriasis therapy. J Drugs Dermatol 2009; 8 (8 Suppl): s4–s8.
- 3 Quigley DA, To MD, Pérez-Losada J et al. Genetic architecture of mouse skin inflammation and tumour susceptibility. Nature 2009; 458: 505–508.
- 4 Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol 2008; 8: 685–698.
- 5 von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Odum N, Geisler C. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat Immunol 2010; 11: 344–349.
- 6 Palmer MT, Lee YK, Maynard CL et al. Lineage-specific effects of 1,25-dihydroxyvitamin D3 on the development of effector CD4 T cells. J Biol Chem 2011; 286: 997–1004.
- 7 Schauber J, Dorschner RA, Coda AB et al. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest 2007; 117: 803–811.
- 8 Mebius RE. Vitamins in control of lymphocyte migration. Nat Immunol 2007; 8: 229–230.
- 9 Jeffery LE, Burke F, Mura M et al. 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J Immunol 2009; 183: 5458–5467.
- 10 Zuel-Fakkar NM, Kamel MM, Asaad MK, Mahran MZ, Shehab AA. A study of ApaI and TaqI genotypes of the vitamin D receptor in Egyptian patients with psoriasis. Clin Exp Dermatol 2011; 36: 355–359.
- 11 Dayangac-Erden D, Karaduman A, Erdem-Yurter H. Polymorphisms of vitamin D receptor gene in Turkish familial psoriasis patients. Arch Dermatol Res 2007; 299: 487–491.
- 12 Halsall JA, Osborne JE, Pringle JH, Hutchinson PE. Vitamin D receptor gene polymorphisms, particularly the novel A-1012G promoter polymorphism, are associated with vitamin D3 responsiveness and non-familial susceptibility in psoriasis. Pharmacogenet Genomics 2005; 15: 349–355.
- 13 Ruggiero M, Gulisano M, Peruzzi B et al. Vitamin D receptor gene polymorphism is not associated with psoriasis in the Italian Caucasian population. J Dermatol Sci 2004; 35: 68–70.
- 14 Saeki H, Asano N, Tsunemi Y et al. Polymorphisms of vitamin D receptor gene in Japanese patients with psoriasis vulgaris. J Dermatol Sci 2002; 30: 167–171.
- 15 Okita H, Ohtsuka T, Yamakage A, Yamazaki S. Polymorphism of the vitamin D(3) receptor in patients with psoriasis. Arch Dermatol Res 2002; 294: 159–162.
- 16 Kaya TI, Erdal ME, Tursen U et al. Association between vitamin D receptor gene polymorphism and psoriasis among the Turkish population. Arch Dermatol Res 2002; 294: 286–289.
- 17 Mee JB, Cork MJ. Vitamin D receptor polymorphism and calcipotriol response in patients with psoriasis. J Invest Dermatol 1998; 110: 301–302.
- 18 Rucevic I, Barisic-Drusko V, Glavas-Obrovac L, Stefanic M. Vitamin D endocrine system and psoriasis vulgaris-review of the literature. Acta Dermatovenerol Croat 2009; 17: 187–192.
- 19 Fang Y, van Meurs JB, d’Alesio A et al. Promoter and 3′-untranslated-region haplotypes in the vitamin D receptor gene predispose to osteoporotic fracture: the Rotterdam study. Am J Hum Genet 2005; 77: 807–823.
- 20 Grundberg E, Lau EM, Pastinen T et al. Vitamin D receptor 3′ haplotypes are unequally expressed in primary human bone cells and associated with increased fracture risk: the MrOS Study in Sweden and Hong Kong. J Bone Miner Res 2007; 22: 832–840.
- 21 Pastinen T, Ge B, Gurd S et al. Mapping common regulatory variants to human haplotypes. Hum Mol Genet 2005; 14: 3963–3971.
- 22 Verlaan DJ, Ge B, Grundberg E et al. Targeted screening of cis-regulatory variation in human haplotypes. Genome Res 2009; 19: 118–127.
- 23 Stefanic M, Karner I, Glavas-Obrovac L et al. Association of vitamin D receptor gene polymorphism with susceptibility to Graves’ disease in Eastern Croatian population: case–control study. Croat Med J 2005; 46: 639–646.
- 24 Stefanic M, Papic S, Suver M, Glavas-Obrovac L, Karner I. Association of vitamin D receptor gene 3′-variants with Hashimoto’s thyroiditis in the Croatian population. Int J Immunogenet 2008; 35: 125–131.
- 25 Wigginton JE, Cutler DJ, Abecasis GR. A note on exact tests of Hardy–Weinberg equilibrium. Am J Hum Genet 2005; 76: 887–893.
- 26 Lewontin RC. The Interaction of Selection and Linkage. I. General Considerations; Heterotic Models. Genetics 1964; 49: 49–67.
- 27 Westfall PH, Young SS. Resampling-Based Multiple Testing: Examples and Methods for P-value Adjustment. John Wiley & Sons Inc, New York, NY 1993.
- 28 Purcell S, Neale B, Todd-Brown K et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81: 559–575.
- 29 Ramos-Lopez E, Kurylowicz A, Bednarczuk T, Paunkovic J, Seidl C, Badenhoop K. Vitamin D receptor polymorphisms are associated with Graves’ disease in German and Polish but not in Serbian patients. Thyroid 2005; 15: 1125–1130.
- 30 Rockman MV, Kruglyak L. Genetics of global gene expression. Nat Rev Genet 2006; 7: 862–872.
- 31 Cookson W, Liang L, Abecasis G, Moffatt M, Lathrop M. Mapping complex disease traits with global gene expression. Nat Rev Genet 2009; 10: 184–194.
- 32 Zhang XJ, Huang W, Yang S et al. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet 2009; 41: 205–210.
- 33 Nair RP, Duffin KC, Helms C et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet 2009; 41: 199–204.
- 34 Selvaraj P, Vidyarani M, Alagarasu K, Prabhu Anand S, Narayanan PR. Regulatory role of promoter and 3′ UTR variants of vitamin D receptor gene on cytokine response in pulmonary tuberculosis. J Clin Immunol 2008; 28: 306–313.
- 35 Nejentsev S, Godfrey L, Snook H et al. Comparative high-resolution analysis of linkage disequilibrium and tag single nucleotide polymorphisms between populations in the vitamin D receptor gene. Hum Mol Genet 2004; 13: 1633–1639.
- 36 Ding J, Gudjonsson JE, Liang L et al. Gene expression in skin and lymphoblastoid cells: Refined statistical method reveals extensive overlap in cis-eQTL signals. Am J Hum Genet 2010; 87: 779–789.