Variations in TAP1 and PSMB9 Genes Involved in Antigen Processing and Presentation Increase the Risk of Vitiligo in the Saudi Community

Ahmad H Mufti; Imad A AlJahdali; Nasser A Elhawary; Samar N Ekram; Iman Abumansour; Ikhlas A Sindi; Hind Naffadi; Ezzeldin N Elhawary; Najiah M Alyamani; Ghydda Alghamdi; Wafaa Alosaimi; Ghufran Rawas; Amaal Alharbi; Mohammed T Tayeb

doi:10.2147/IJGM.S341079

Variations in TAP1 and PSMB9 Genes Involved in Antigen Processing and Presentation Increase the Risk of Vitiligo in the Saudi Community

Int J Gen Med. 2021 Dec 19:14:10031-10044. doi: 10.2147/IJGM.S341079. eCollection 2021.

Affiliations

¹ Department of Medical Genetics, College of Medicine, Umm Al-Qura University, Mecca, 21955, Saudi Arabia.
² Department of Community Medicine, College of Medicine, Umm Al-Qura University, Mecca, 21955, Saudi Arabia.
³ Department of Biotechnology, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
⁴ Common Science, First Year Deanship, Umm Al-Qura University, Mecca, Saudi Arabia.
⁵ MS Genomic Medicine Program, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
⁶ Department of Biology, College of Science, University of Jeddah, Jeddah, Saudi Arabia.
⁷ Department of Hematology, Maternity and Children Hospital, Mecca, Saudi Arabia.
⁸ King Abdullah Medical City, Mecca, Saudi Arabia.
⁹ Saudi Biobank National ProjectKing Abdullah International Medical Research Center, Jeddah, Saudi Arabia.

Abstract

Background: The antigen processing 1 (TAP1) and proteasome 20S subunit beta 9 (PSMB9) genes are associated with strong susceptibility to many autoimmune diseases. Here, we explored whether TAP1/PSMB9 genetic variants, individually or combined, affected susceptibility to the complex, autoimmune-based skin disorder vitiligo.

Methods: Samples of genomic DNA from buccal cells of 172 patients with vitiligo and 129 healthy controls were analyzed using TaqMan™ genotyping assays for the TAP1 rs1135216 (A>G) and PSMB9 rs17587 (A>G) single nucleotide polymorphisms (SNPs). SNPStats software (https://www.snpstats.net) was utilized to choose the best interactive inheritance mode for selected SNPs.

Results: The genotype frequencies for the TAP1 rs1135216 and PSMB9 rs17587 SNPs were in Hardy-Weinberg equilibrium for cases (P= 0.11 and P= 0.10, respectively) but not for controls (P< 0.05). The TAP1 rs1135216 (D637G) and PSMB9 rs17587 (R60H) SNPs increased the risk of vitiligo four-fold and two-fold, respectively (odds ratio [OR]= 4.6; 95% confidence interval [CI], 3.2-6.5; P< 0.0001 and OR= 2.2; 95% CI, 1.5-3.1; P< 0.0001). The recessive model (G/G-D/G versus D/D) and the codominant model (R/R versus R/H) were the best models of inheritance for the rs113526 and rs17587 SNPs, respectively (OR= 16.4; 95% CI, 2.0-138; P= 0.0006 and OR= 1.7; 95% CI, 0.3-1.8; P= 0.013). Vulgaris, focal vulgaris, and acryl/acrofacial were the most common vitiligo subtypes in our sample (51%, 21%, and 19%, respectively). Heterozygous rs113526 (637D/G) and rs17587 (60R/H) were the most common genotypes in most vitiligo subtypes. The heterozygous 637D/G genotype and the 637G variant allele were significantly more common in patients with active disease than in patients with stable disease (P= 0.000052 and P= 0.0063, respectively).

Conclusion: Our findings suggest a crucial role for TAP1 rs1135216 and PSMB9 rs17587 in the risk and progression of vitiligo in the Saudi community. Genomic analyses are needed to identify more candidate genes and more genetic variants associated with vitiligo.

Keywords: TAP1/PSMB9; TaqMan genotyping; linkage disequilibrium; single nucleotide polymorphisms; vitiligo.

Grants and funding

This work was funded by the Deanship of Scientific Research, Umm Al-Qura University, Mecca, Saudi Arabia, under grant 19-MED-1-01-0033.