Effect of glutathione S-transferase polymorphisms and proximity to hazardous waste sites on time to systemic lupus erythematosus diagnosis: results from the Roxbury lupus project.
OBJECTIVE
The high prevalence of systemic lupus erythematosus (SLE) among African American women may be due to environmental exposures, genetic factors, or a combination of factors. Our goal was to assess association of residential proximity to hazardous waste sites and genetic variation in 3 glutathione Stransferase (GST) genes (GSTM1, GSTT1, and GSTP1) with age at diagnosis of SLE.


METHODS
Residential histories were obtained by interviewing 93 SLE patients from 3 predominantly African American neighborhoods in Boston. Residential addresses and locations of 416 hazardous waste sites in the study area were geocoded using ArcView software. Time-varying Cox models were used to study the effect of residential proximity to hazardous sites, GST genotype, and interaction between genotype and exposure in determining age at diagnosis.


RESULTS
The prevalence of SLE among African American women in these neighborhoods was 3.56 SLE cases per 1,000. Homozygosity for GSTM1-null and GSTP1 Ile105Val in combination was associated with earlier SLE diagnosis (P = 0.03), but there was no association with proximity to 416 hazardous sites. Available data on specific site contaminants suggested that, at a subset of 67 sites, there was higher potential risk for exposure to volatile organic compounds (P < 0.05 with Bonferroni correction). GST genotypes had a significant interaction with proximity (P = 0.03) in analyses limited to these sites.


CONCLUSIONS
There was no independent association between residential proximity to hazardous waste sites and the risk of earlier SLE diagnosis in this urban population. However, analysis of a limited number of sites indicated that the risk of earlier SLE associated with proximity to hazardous sites might be modulated by GST polymorphisms.
Karlson
Elizabeth W
EW
Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. ekarlson@partners.org
Watts
Julie
J
Signorovitch
James
J
Bonetti
Marco
M
Wright
Elizabeth
E
Cooper
Glinda S
GS
McAlindon
Timothy E
TE
Costenbader
Karen H
KH
Massarotti
Elena M
EM
Fitzgerald
Lisa M
LM
Jajoo
Ramina
R
Husni
M Elaine
ME
Fossel
Anne H
AH
Pankey
Helen
H
Ding
Wei-Zi
WZ
Knorr
Robert
R
Condon
Suzanne
S
Fraser
Patricia A
PA
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000208:ethnology / Q000706:statistics & numerical data; D000368:Aged; D001900:Boston / Q000453:epidemiology; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006256:Hazardous Waste / Q000009:adverse effects*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000208:ethnology / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors
D006256:Hazardous Waste; D005982:Glutathione Transferase