Polymorphisms in XPD (Asp312Asn and Lys751Gln) genes, sunburn and arsenic-related skin lesions.
BACKGROUND
Single-nucleotide polymorphisms in genes related to DNA repair capacity and ultraviolet exposure have not been well investigated in relation to skin lesions associated with arsenic exposure. This population based case-control study, of 600 cases and 600 controls, frequency matched on age and gender in Pabna, Bangladesh, in 2001-2002, investigated the association and potential effect modification between polymorphisms in Xeroderma Pigmentosum complementation group D (XPD) (Lys751Gln and Asp312Asn) genes, tendency to sunburn and arsenic-related skin lesions.


METHODS
Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).


RESULTS
No significant association was observed between skin lesions and the XPD 312 Asp/Asn (adjusted OR = 0.87, 95% CI = 0.65-1.15) Asn/Asn (adjusted OR = 0.76, 95% CI = 0.50-1.15) (referent Asp/Asp); XPD 751 Lys/Gln (adjusted OR = 0.92, 95% CI = 0.69-1.23) Gln/Gln (adjusted OR = 0.98, 95% CI = 0.66-1.45) (referent Lys/Lys). While we did not observe any evidence of effect modification of these polymorphisms on the association between well arsenic concentration and skin lesions, we did observe effect modification between these polymorphisms and sunburn tendency and arsenic-related skin lesions. Individuals with the heterozygote or homozygote variant forms (Asp/Asn or Asn/Asn) had half the risk of skin lesions (OR = 0.45, 95% CI = 0.29-0.68) compared with those with the wild-type XPDAsp312Asn genotype (Asp/Asp) and individuals with heterozygote or homozygote variant forms (Lys/Gln or Gln/Gln) had half the risk of skin lesions (OR = 0.47, 95% CI = 0.31-0.72) compared with those with the wild-type XPDLys751Gln genotype (Lys/Lys), within the least sensitive strata of sunburn severity. We observed effect modification on the multiplicative scale for XPD 751 and XPD 312.


CONCLUSIONS
XPD polymorphisms modified the relationship between tendency to sunburn and skin lesions in an arsenic exposed population. Further study is necessary to explore the effect of XPD polymorphisms and sun exposure on risk of arsenic-related skin lesions.
McCarty
Kathleen M
KM
Department of Epidemiology and Public Health, Division of Environmental Health Sciences, Yale University School of Medicine, Epidemiology and Public Health, New Haven, CT, 06520 USA. kathleen.mccarty@yale.edu
Smith
Thomas J
TJ
Zhou
Wei
W
Gonzalez
Ernesto
E
Quamruzzaman
Quazzi
Q
Rahman
Mahmuder
M
Mahiuddin
Golam
G
Ryan
Louise
L
Su
Li
L
Christiani
David C
DC
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D001151:Arsenic / Q000009:adverse effects* / Q000032:analysis; D001216:Asparagine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005973:Glutamine / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012871:Skin Diseases / Q000139:chemically induced / Q000235:genetics*; D013471:Sunburn / Q000235:genetics*; D014881:Water Supply / Q000032:analysis; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D005973:Glutamine; D001224:Aspartic Acid; D001216:Asparagine; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D008239:Lysine; D001151:Arsenic