Nuclear Factor Erythroid-2-related Factor 2 Gene Polymorphisms in Vitiligo.

BACKGROUND: Oxidative stress is now one of the accepted theories of vitiligo development. Nuclear factor erythroid-2-related factor 2 (Nrf2) regulates the expression of antioxidant proteins. OBJECTIVE: This work aimed to evaluate the association of Nrf2 gene polymorphisms with the susceptibility to vitiligo among a sample of Egyptian patients with vitiligo. METHODS: This case-control study included 100 patients with vitiligo and 50 healthy matched volunteers serving as a control group. Genotyping was carried out by real-time polymerase chain reaction. RESULTS: The frequencies of TT, CT, and combined (TT+CT) genotypes and the T allele of Nrf2 (rs35652124) were significantly increased in the studied patients with vitiligo relative to the healthy controls (p<0.001, p=0.012, p<0.001 and p<0.001, respectively). There was a nonsignificant difference between patients and controls regarding Nrf2 (rs6721961) genotypes. However, the T allele of Nrf2 (rs6721961) was significantly predominant in the studied patients compared to in the controls (p=0.029). Among the studied criteria, the T allele of Nrf2 (rs6721961) was predominant in patients with a marginal type of repigmentation (p=0.022), while the G allele of the same single-nucleotide polymorphism was associated with a higher body mass index value (p=0.034). One hundred percent of patients with vitiligo with the Nrf2 (rs6721961) GT genotype had a progressive disease course (p=0.015). CONCLUSION: Nrf2 (-617 T/G) and (-653 T/C) polymorphism might play a role in patient susceptibility to vitiligo and modify the clinical presentation of the disease.

DEFB1 gene polymorphisms modify vitiligo extent and response to NB-UVB phototherapy.

Human beta defensin-1(hBD-1); an antimicrobial peptide, has immune regulatory effects which may be involved in autoimmunity. The aims were to evaluate the association between defensin beta 1 (DEFB1) (-44 C/G) and (-20 G/A) gene polymorphisms with the risk of vitiligo development, the extent of the disease and the response to NB-UVB treatment in a sample of Egyptian population. 178 active nonsegmental vitiligo patients and 182 control subjects were included in this prospective case control study. Vitiligo extent was evaluated using vitiligo area scoring index (VASI). Gene polymorphisms in all participants were studied by RFLP PCR technique. Patients were treated by three narrowband UVB (NB-UVB) treatment sessions per week. After 12 weeks, the patients were reevaluated clinically to assess the extent of the disease using VASI scoring again and to evaluate the type of repigmentation, if any. AA genotype of DEFB1 (-20G/A) has a protective role against vitiligo development, while (DEFB1 -44 C/G) GG genotype and G allele increase the risk of vitiligo development about two folds. Patients carrying polymorphism in DEFB1 (-20G/A) only showed the lowest VASI scores (14.23 ± 2.77) and the highest percentage of improvement (66.12 ± 18.01%), while patients carrying polymorphism in DEFB1(-44 C/G) only showed the highest baseline VASI scores (38.87 ± 6.7) and the lowest therapeutic response (23.79 ± 19.42%) among all patients groups. Different DEFB1 gene polymorphisms may modify the risk of vitiligo development, the disease extent and the response to NB-UVB phototherapy.

Proteasome Subunit Beta Type-8 (PSMB8) Gene Polymorphisms in Vitiligo: A Possible Predictor of Auditory Involvement.

INTRODUCTION: Proteasome subunit beta type-8 (PSMB8) is a protein that contributes to the complete assembly of 20S proteasome complexes, which play a role in the pathogenesis of vitiligo. OBJECTIVE: The study aimed to evaluate the association between PSMB8 gene polymorphisms with vitiligo to assess its clinical significance among a sample of Egyptian patients with vitiligo. METHODS: Genomic DNA was isolated from blood samples of 100 patients with vitiligo and 100 control subjects, and detection of PSMB8 polymorphisms was done by real-time PCR. Data analysis was carried out for the entire cohort. Statistics were performed using software. Audiological evaluation was performed, including pure-tone audiometry, extended high-frequency audiometry, transient evoked otoacoustic emissions, and auditory brainstem response. RESULTS: There was a significant difference between PSMB8 genotypes and alleles distribution in patients and control groups. Ten percent of the study sample had sensorineural hearing loss. The patients with hearing loss were significantly older (P=0.0002), had significantly later age of onset (P=0.0007), longer duration (P=0.0021), higher body mass index (BMI) (P=0.045), and higher vitiligo area scoring index (VASI) scores (P=0.0015). All patients had extensive forms of vitiligo (generalized and universal). Regarding the VIT rs2071543 polymorphism, all of the patients with hearing loss were carrying the CA and AA genotypes. None of the patients carried the reference genotype, CC. The A allele of VIT rs2071543 was significantly associated with hearing affection (P=0.024). CONCLUSION: In our study, PSMB8 polymorphism was associated with the susceptibility to develop vitiligo and appeared to have clinical significance among the studied group of patients. Factors predicting auditory abnormalities should be further studied for early detection and management.