DOI: 10.4103/idoj.idoj_1287_25 ISSN: 2229-5178
Pharmacogenomic Markers of Disease Susceptibility and Glucocorticoid Responsiveness in Pemphigus Vulgaris
Deepika Pandhi, Rajashri Kar, Bharti Aggarwal, Diwesh Chawla Abstract
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.