Xenobiotic-metabolizing genes and small-for-gestational-age births: interaction with maternal smoking.
BACKGROUND
Little is known about the role of xenobiotic-metabolizing gene variants as risk factors for small-for-gestational-age (SGA) births or as modifiers for the effects of exposures such as maternal smoking.


METHODS
We conducted 2 joint studies: a case-control design including 493 cases (birth weight below the 10th percentile according to gestational age and sex) and 472 controls (at or above the 10th percentile) and a family-based study (mother, father, and newborn) with approximately 250 case trios and a similar number of control trios. Logistic regression and a log-linear model were used to analyze the association between genetic variants such as CYP1A1*2A, CYP1A1*2B, CYP1A1*4, GSTT1, GSTM1, and XRCC3 and SGA. The interaction between genetic variants and maternal smoking was also studied.


RESULTS
The odds ratio (OR) for the association of complete maternal GSTT1 deletion with SGA was 0.63 (95% confidence interval = 0.41-0.97), and that for the complete newborn GSTM1 deletion was 0.74 (0.55-0.98). Newborns with the partial GSTT1 deletion had an OR of 1.40 (1.01-1.95), and newborns homozygous for CYP1A1*2A had an OR of 4.28 (1.02-18.0). These results were coherent with the trio-based results. Significant interactions were observed between maternal smoking in the third trimester and CYP1A1*2A (P = 0.03), XRCC3 (P = 0.03), and newborn GSTT1 (P = 0.01).


CONCLUSIONS
Certain genetic variants involved in the metabolism of xenobiotics increase the risk of SGA, as well as modify the effects of maternal smoking by increasing or decreasing its risk.
Infante-Rivard
Claire
C
Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montréal, Québec, Canada. claire.infante-rivard@mcgill.ca
Weinberg
Clarice R
CR
Guiguet
Marguerite
M
D000328:Adult; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects*; D015262:Xenobiotics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; D015262:Xenobiotics; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase