Dataset Information

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

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.

SUBMITTER: Mufti AH

PROVIDER: S-EPMC8702990 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAutoimmunity has been implicated in the destruction of melanocytes from vitiligo skin. Major histocompatibility complex (MHC) class-II linked genes proteasome subunit beta 8 (PSMB8) and transporter associated with antigen processing 1 (TAP1), involved in antigen processing and presentation have been reported to be associated with several autoimmune diseases including vitiligo.ObjectivesTo explore PSMB8 rs2071464 and TAP1 rs1135216 single nucleotide polymorphisms and to estimate the expression of PSMB8 and TAP1 in patients with vitiligo and unaffected controls from Gujarat.MethodsPSMB8 rs2071464 polymorphism was genotyped using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) and TAP1 rs1135216 polymorphism was genotyped by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in 378 patients with vitiligo and 509 controls. Transcript levels of PSMB8 and TAP1 were measured in the PBMCs of 91 patients and 96 controls by using qPCR. Protein levels of PSMB8 were also determined by Western blot analysis.ResultsThe frequency of 'TT' genotype of PSMB8 polymorphism was significantly lowered in patients with generalized and active vitiligo (p = 0.019 and p = 0.005) as compared to controls suggesting its association with the activity of the disease. However, TAP1 polymorphism was not associated with vitiligo susceptibility. A significant decrease in expression of PSMB8 at both transcript level (p = 0.002) as well as protein level (p = 0.0460) was observed in vitiligo patients as compared to controls. No significant difference was observed between patients and controls for TAP1 transcripts (p = 0.553). Interestingly, individuals with the susceptible CC genotype of PSMB8 polymorphism showed significantly reduced PSMB8 transcript level as compared to that of CT and TT genotypes (p = 0.009 and p = 0.003 respectively).ConclusionsPSMB8 rs2071464 was associated with generalized and active vitiligo from Gujarat whereas TAP1 rs1135216 showed no association. The down-regulation of PSMB8 in patients with risk genotype 'CC' advocates the vital role of PSMB8 in the autoimmune basis of vitiligo.

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