CYP1A2*1F and GSTM1 alleles are associated with susceptibility to porphyria cutanea tarda.
Porphyria cutanea tarda (PCT) is a cutaneous porphyria with sporadic (type 1) and familial (type 2) subtypes, both resulting from decreased hepatic uroporphyrinogen decarboxylase (UROD) activity. Environmental and genetic factors are involved in the development of PCT, and genetic variants in the cytochrome P450 (CYP ) genes, CYP1A1 and CYP1A2, have been implicated. We investigated the association between PCT and variants in CYP1A1, CYP1A2 and CYP2E1, and the glutathione-S-transferase (GST ) genes, GSTM1 and GSTT1. PCT diagnosis was based on urinary or plasma porphyrin profiles. Patients were classified as type 1 or 2 PCT based on UROD mutation analysis. The CYP1A2*1F promoter A allele frequency was significantly higher (P < 0.022) and the A/A genotype frequency marginally higher in PCT patients overall (P < 0.057), with the A/A genotype significantly more common in type 1 PCT (P < 0.043). The presence of the wild-type GSTM1 allele also was associated significantly with PCT (P < 0.019). Neither hemochromatosis (HFE) mutations, tobacco smoking, hepatitis C and HIV infection, ethanol consumption, nor estrogen use were associated with these allelic variants. Age at onset was significantly lower in type 2 PCT patients (P < 0.001), as observed previously. Thus, positive associations between PCT and the CYP1A2*1F promoter A allele and A/A genotype and the wild-type GSTM1 allele indicates that these functional hepatic biotransformation enzymes are risk factors for the development of this disease.
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas 77555-1109, United States of America.
Jeffrey K
JK
Wickliffe
Sherif Z
SZ
Abdel-Rahman
Chul
C
Lee
Csilla
C
Kormos-Hallberg
Gagan
G
Sood
Catherine M
CM
Rondelli
James J
JJ
Grady
Robert J
RJ
Desnick
Karl E
KE
Anderson
D000483:Alleles; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D015810:Linkage Disequilibrium; D017119:Porphyria Cutanea Tarda / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors
D019388:Cytochrome P-450 CYP1A2; D005982:Glutathione Transferase; D007527:Isoenzymes