Pharmacogenomic Markers of Disease Susceptibility and Glucocorticoid Responsiveness in Pemphigus Vulgaris

BACKGROUND: Response to glucocorticoid (GC) therapy in pemphigus vulgaris (PV) is variable and may be influenced by pharmacogenomic factors. This study aimed to evaluate the association between glutathione S-transferases (GST) gene polymorphisms and Multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) variations with steroid responsiveness in PV patients and evaluate their role in conferring susceptibility to PV. PATIENTS AND METHODS: Eighty participants were included: Group A: GC responders (n = 20), Group B: GC nonresponders (n = 20), Group A+B: Combined PV cases (n = 40), and Group C: healthy controls (n = 40). Disease severity was assessed using the Pemphigus Disease Area Index and Dermatology Life Quality Index. Glutathione S-transferase (GST) genotypes, GSTM1, GSTT1, and GSTP1, were analyzed by multiplex polymerase chain reaction (PCR); MDR1 2677G>A/T single nucleotide polymorphism was evaluated by amplification refractory mutation system PCR. MDR1 gene mRNA expression was quantified by reverse transcription-PCR using 18S rRNA as a housekeeping gene. RESULTS: Among the 40 PV patients (mean age: 41.3 ± 13 years; male:female = 21:19), GSTM1 heterozygosity was significantly more frequent (45%) than in controls (28%) (P = 0.01; odds ratio = 4.636), suggesting its role as a risk factor. GSTT1 heterozygosity was more prevalent in controls (Group C; 58%) than in cases (Group A+B) (32%; P = 0.04), indicating a potential protective role. Among PV patients, nonresponders (Group B) had higher (though statistically non-significant) GSTT1 heterozygosity and combined variant genotypes, and GSTM1 heterozygosity was more frequent in responders (Group A). MDR1 genotype distribution (2677G>A/T) did not differ significantly between groups (A and B); however, downregulated MDR1 mRNA expression was evident in Group A and Group B compared to Group C. LIMITATIONS: Small sample size, technical variability in mRNA quantification, and single-population analysis. CONCLUSION: Heterozygosity in GSTM1 and GSTT1 may influence PV susceptibility and steroid responsiveness. MDR1 expression may correlate with treatment response but requires validation using stable reference genes.