Nicotine metabolizing genes GSTT1 and CYP1A1 in sudden infant death syndrome.
Exposure to tobacco, both to the developing fetus as well as in the postnatal period, has been identified as a key risk factor in the etiology of sudden infant death syndrome (SIDS). Polymorphisms in both the GSTT1 and CYP1A1 genes have been reported to impact the metabolic detoxification process for cigarette smoke and have been associated with low birth weight. Thus, expression of polymorphisms in these genes may account for the varying susceptibility to the adverse health consequences of tobacco exposure, including SIDS. We hypothesized that functional polymorphisms in GSTT1 (gene deletion) and CYP1A1 (m1, m2, and m3) might be associated with SIDS risk. DNA was prepared from 106 SIDS cases and 106 ethnicity- and gender-matched controls using standard methods. Regions of interest were amplified using PCR, subjected to enzyme digestion, and analyzed on agarose gel. No association was observed between the GSTT1 gene deletion or the CYP1A1 m1, m2, and m3 polymorphisms with SIDS risk when considered independently or in combination. These results indicate that the GSTT1 gene deletion and polymorphisms of CYP1A1 are not responsible for increased SIDS risk in our dataset. However, because SIDS cases with confirmed history of nicotine exposure were limited (7/106 cases), a relationship that might be apparent in a cohort with a large subset of SIDS cases with known history of nicotine exposure cannot be ruled out. A prospective study of SIDS cases with nicotine exposure history is necessary to resolve the relationship between nicotine metabolizing genes and SIDS.
Rand
Casey M
CM
Department of Pediatrics, Rush Children's Hospital at Rush University Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, USA.
Weese-Mayer
Debra E
DE
Maher
Brion S
BS
Zhou
Lili
L
Marazita
Mary L
ML
Berry-Kravis
Elizabeth M
EM
D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009538:Nicotine / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013398:Sudden Infant Death / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D014028:Tobacco Smoke Pollution
D014028:Tobacco Smoke Pollution; D009538:Nicotine; D019363:Cytochrome P-450 CYP1A1; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase