VDR polymorphisms ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) in Pakistani vitiligo patients and controls

Sumaira Sajjad, Saeeda Munir, Simeen Ber Rahman, Nusrat Saba, Sadia Rehman

Abstract


Objective To understand the role of three single nucleotide polymorphisms (SNP) of vitamin D receptor (VDR) gene rs7975232, rs731236 and rs2228570 in Pakistani vitiligo patients and ethnically matched controls.

 

Methods 196 vitiligo patients and 262 controls were included in this study. Genomic DNA was extracted and polymerase chain reaction, restriction length polymorphism (PCR-RFLP) was done.

 

Results Genotype CA (rs7975232) was found to be associated with susceptibility (Odd ratio=1.46, 95% CI=1.01-2.13, p=0.046) and TT genotype (rs731236) with protection (Odd ratio=0.48, 95% CI=0.25-0.92, p=0.003) to vitiligo. TT genotype for rs731236 was significantly high in controls and absent in undetermined/unclassified group of patients. Vitiligo patients and controls were also compared on the basis of gender. Genotype CA (OR=2.12, 95% CI=1.18-3.79, p=0.013) and CC (OR =0.21 95% CI=0.06-0.73, p=0.007) for rs7975232 were significantly high in male patients and controls, respectively. For rs2228570 CC genotype was significantly high in controls (OR=0.52, 95% CI=0.2-0.97), p=0.04) while TC genotype showed significant difference between patient and controls (OR=1.93, 95% CI=1.02-3.6), p=0.05). In combined effect haplotype A-T-C was found significantly high in controls as compared with the patients (Odd ratio=0.57, 95% CI=0.34-0.97, p=0.04).

 

Conclusion VDR polymorphisms may be involved in etiology of vitiligo and future studies should be design to screen large sample size for more VDR polymorphism to get more precise picture.

 


Keywords


Vitamin D receptor, vitiligo, polymorphism, polymerase chain reaction, restriction length polymorphism

Full Text:

PDF

References


Alikhan A, Felsten L.M, Daly M et al. Vitiligo: a comprehensive overview part 1. Introduction, epidemiology, quality of life, diagnosis, associations, histopathology, etiology, and work up. J Am Acad Dermatol. 2011;65:473-91.

Halder, Chappell. Vitiligo update. Semin Cutan Med Sur. 2009;28 (2):86-92.

Sandoval-Cruz M, Garcia-Carrasco M, Sanchez-Porras R, Mendoza-Pinto C, Jiménez-Hernández M, Munguía-Realpozo P et al. Immunopathogenesis of vitiligo. Autoimmun Rev. 2011;10:762-5.

Schallreuter KU, Bahadoran P, Picardo M, Slominski A, Elassiuty YE, Kemp EH et al. Vitiligo pathogenesis: autoimmune disease, genetic defect, excessive reactive oxygen species, calcium imbalance, or what else? Exp Dermatol. 2008;17:139-40; discussion 41-60.

Tarlé RG, Mira MT. Vitiligo - Part 1. An Bras Dermatol. 2014;89:465-66.

Saleh HMA, Abdel Fattah NSA, Hamza H-T. Evaluation of serum 25-hydroxyvitamin D levels in vitiligo patients with and without autoimmune diseases. Photodermatol Photoimmunol Photomed. 2013;29:34-40.

Cantorna MT, Yu S, Bruce D. The paradoxical effects of vitamin D on type 1 mediated immunity. Mol Aspects Med. 2008;29:369-75.

Oh SH, Kim M. Vitamin D and vitiligo. In: Park KK, editor. Vitiligo - Management and Therapy. Shanghai: InTech China; 2011.

Adorini L, Penna G. Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol. 2008;4:404-12.

Pardue SL, Fite KV, Bengston L, Lamont SJ, Boyle ML 3rd, Smith JR Jr. Enhanced integumental and ocular amelanosis following the termination of cyclosporine administration. J Invest Dermatol. 1987;88:758-61.

Juturka PW, Pemus LS, Whitefield GK, Thompson PD, Hsieh JC, Zitzer H et al. The polymorphic N terminus in human vitamin D receptor isoforms influences transcriptional activity by modulating interaction with transcription factors IIB. Mol Endocrinol. 2000;14:401-2.

Kostner K, Denzer N, Muller CSL, Klein R, Tilgen R, Reichrath J. The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer. Anticancer Res. 2009;29:3511-36.

Langdahl BL, Gravholt CH, Brixen K, Eriksen EF. Polymorphism in the Vitamin D receptor gene and bone mass, bone turnover and osteoporotic fractures. Euro J Clin Invest. 2000;30:608-17.

Han JA, Colditz G, Hunter JD. Polymorphisms in the MTHFR and VDR genes and skin cancer risk Carcinogenesis. 2007;28:390-7.

Bid HK, Konwar R, Aggarwal CG, Gautam S, Saxena M, Nayak VL et al. Vitamin D receptor (fokI, bsmI and taqI) gene polymorphisms and type 2 diabetes mellitus: a North Indian study. Indian J Med Sci. 2009;63:187-94.

Acikbas I, San B, Tepeli E, Ergin S, Aktan S, Bagci H. Vitamin D receptor gene polymorphisms and haplotypes (Apa I, Bsm I, Fok I, Taq I) in Turkish psoriasis patients. Med Sci Monit. 2012;18:661-6.

Mohapatra S, Saxena A, Gandhi G, Koner BC, Ray PC. Vitamin D and VDR gene polymorphism (FokI) in epithelial ovarian cancer in Indian population. J Ovarian Res. 2013;26:37.

Uitterlinden AG, Fang Y, Joyce BJ, Pols HA, Van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Genes. 2004;338:143-56.

Sambrook J, Russell DW. Molecular Cloning: A Laboratory Manual. 3rd edn. New York: Cold Spring Harbor Laboratory Press; 2001.

Pani MA, Knapp M, Donner H, Braun J, Baur MP, Usadel KH et al. Vitamin D receptor Allele combinations influence genetic susceptibility to type 1 diabetes in Germans. Diabetes. 2000;49:504-7.

Al-Shobaili HA. Update on the genetics characterization of vitiligo. J health Sci Qassim University. 2011;5:172-9.

Takci Z, Tekin Ö, Ertuğru DT, Karadağ AS, Akin KO. A case-control study: evaluation of vitamin D metabolism in patients with vitiligo. Turk J Med Sci. 2015;45:837-41.

Khurrum H, Al Ghamdi KM. The relationship between the serum level of vitamin D and vitiligo: A controlled study on 300 subjects. J Cutan Med Surg. 2016;20:139-40.

Beheshti A, Ghadami H, Barikani A, Haj Manouchehri F. Assessment of vitamin D plasma levels in patients with vitiligo vulgaris. Acta Med Iran. 2014;52:601-6.

Ustun I, Seraslan G, Gokce C, Motor S, Can Y, Ugur Inan M et al. Investigation of vitamin D levels in patients with vitiligo vulgaris. Acta Dermatovenerol Croat. 2014;22:110-3.

Sehrawat M, Arora TC, Chauhan A, Kar HK, Poonia A, Jairath V. Correlation of vitamin D levels with pigmentation in vitiligo patients treated with NBUVB therapy. ISRN Dermatol. 2014;2014:493213. doi: 10.1155/2014/493213.

AlGhamdi K, Kumar A, Moussa N. The role of vitamin D in melanogenesis with an emphasis on vitiligo. Indian J Dermatol Venereol Leprol. 2013;79:750-8.

Sheth VM, Guo Y, Qureshi AA. Comorbidities associated with vitiligo: a ten-year retrospective study. Dermatology. 2013;227:311-5.

Silverberg JI, Silverberg AI, Malka E, Silverberg NB. A pilot study assessing the role of 25 hydroxy vitamin D levels in patients with vitiligo vulgaris. J Am Acad Dermatol. 2010;62:937-41.

Birlea S, Birlea M, Cimponeriu D, Apostol P et al. Autoimmune diseases and vitamin D receptor Apa-I polymorphism are associated with vitiligo in a small inbred Romanian Community. Acta Derm Venereol. 2006;86:209-14.

Li K, Shi Q, Yang L, et al. The association of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels with generalized vitiligo. Br J Dermatol. 2012;167:815-21.

Aydıngöz IE, Bingül I, Doğru-Abbasoğlu S, Vural P, Uysal M. Analysis of vitamin D receptor gene polymorphisms in vitiligo. Dermatology. 2012;224:361-8.

Li L, Wu Y, Li L, Cai YF, Geng L, Gao XH et al. Association of ApaI and BsmI polymorphisms with vitiligo risk: a meta-analysis. Clin Exp Dermatol. 2015;40:794-803.


Refbacks

  • There are currently no refbacks.


ISSN: 1560-9014