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Association of genetic variants of xenobiotic metabolic pathway with systemic lupus erythematosus

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Title Association of genetic variants of xenobiotic metabolic pathway with systemic lupus erythematosus
 
Creator Rupasree, Yedluri
Naushad, Shaik Mohammad
Rajasekhar, Liza
Kutala, Vijay Kumar
 
Subject Systemic lupus erythematosus
Cytochrome P450 1A1
Catecholamine-O-methyl transferase
Glutathione-S-transferase
Genetic variant
Polymorphism
Xenobiotic metabolic pathway
 
Description 447-452
In view of
documented evidence that catechol estrogen-DNA adducts serve as epitopes for
binding of anti-nuclear antibodies, genetic polymorphisms of the xenobiotic
metabolic pathway involved in estrogen metabolism might contribute towards
pathophysiology of systemic lupus erythematosus (SLE). To test this hypothesis,
a case-control study was conducted. Cytochrome P 450 1A1 (CYP1A1) m4 (OR: 4.93,
95% CI: 1.31-18.49), catecholamine-o-methyl transferase (COMT) H108L (OR: 1.39,
95% CI: 1.03-1.88) and glutathione-S-transferase (GST) T1 null (OR: 1.83, 95%
CI: 1.11- 3.01) variants showed association with SLE risk. SHEsis web-based
platform analysis showed mild to moderate linkage disequilibrium between the
CYP1A1 m1, m2 and m4 variants (D’: 0.19-0.37). Among the different haplotypes
of CYP1A1, CAC-haplotype harboring CYP1A1 m1 variant showed association with
SLE risk (OR: 1.46, 95% CI: 1.11-1.92). Multifactor dimensionality reduction
analysis (MDR) showed potential gene-gene interactions between the phase II
variants i.e. COMT H108L × GSTT1 null × GSTM1 null (p<0.0001) and
also between the phase II and I variants i.e. COMT
H108L × GSTT1 null × CYP1A1 m1 × CYP1A1 m2 in inflating the risk of SLE by
3.33-folds (95% CI: 2.30-4.82) and 4.00-folds (95% CI: 2.77-5.78),
respectively. To conclude, hyperinducibility of CYP1A1 due to m1 and m4
variants and defective phase-II detoxification due to COMT H108L and GSTT1 null
variants increase the susceptibility to SLE.
 
Date 2013-10-26T09:49:51Z
2013-10-26T09:49:51Z
2013-10
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/22642
 
Language en_US
 
Rights CC Attribution-Noncommercial-No Derivative Works 2.5 India
 
Publisher NISCAIR-CSIR, India
 
Source IJBB Vol.50(5) [October 2013]