Disinfection by-products exposure and intra-uterine growth restriction: Do genetic polymorphisms of CYP2E1or deletion of GSTM1 or GSTT1 modify the association?
Exposure to disinfection by-products (DBPs) during pregnancy was associated with reduced foetal growth. Genetic susceptibility might play a role, especially for genes encoding for the Cytochrome P450 (CYP2E1) and Glutathione S-Transferase (GST) enzymes, involved in metabolism and activation of DBPs. Few epidemiological studies evaluated these gene-environment interactions and their results were never replicated.



This study aims to examine interactions between trihalomethanes (THM) or haloacetic acids (HAA) exposure and genetic polymorphisms on small for gestational age (SGA) neonates by investigating single nucleotide polymorphisms (SNPs) in CYP2E1 gene and GSTM1 and GSTT1 deletions in mothers-children pairs.



A population-based case-control study of 1549 mothers and 1455 children was conducted on SGA and THM/HAA exposure. DNA was extracted from blood or saliva cells. Targeted SNPs and deletions were genotyped. Statistical interaction between SNPs/deletions and THMs or HAAs in utero exposure with regard to SGA occurrence was evaluated by unconditional logistic regression with control of potential confounders.



Previously reported positive modification of the effect of THM uterine exposure by mothers or newborns CYP2E1 rs3813867 C allele or GSTM1 deletion was not replicated. However interactions with CYP2E1 rs117618383 and rs2515641 were observed but were not statistically significant after correction for multiple testing.



Previous positive interactions between THMs exposure and CYP2E1 and GSTM1 were not replicated but interactions with other CYP2E1 polymorphisms are reported.
Direction de la santé environnementale et de la toxicologie, Institut national de santé publique du Québec, Département de médecine sociale et préventive, Faculté de médecine, Université Laval and Axe Santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec City, Québec G1V 7B3, Canada. Electronic address: patrick.levallois@msp.ulaval.ca.
Patrick
P
Levallois
Département de biologie moléculaire, de biochimie médicale et de pathologie, Faculté de médecine, Université Laval and Axe Reproduction, santé de la mère et de l'enfant, Centre de recherche du CHU de Québec, Québec City, Québec G1L 3L5, Canada. Electronic address: yves.giguere@fmed.ulaval.ca.
Yves
Y
Giguère
Centre de Recherche Clinique et Évaluative en Oncologie. Hôtel-Dieu de Québec, CHU de Québec-Université Laval, Québec City, Québec G1R 3S1, Canada. Electronic address: moliere.nguile@gmail.com.
Molière
M
Nguile-Makao
École supérieure d'aménagement du territoire and Chaire d'eau potable, Université Laval, Québec City, Québec G1V 0A6, Canada. Electronic address: manuel.rodriguez@esad.ulaval.ca.
Manuel
M
Rodriguez
Direction de la santé environnementale et de la toxicologie, Institut national de santé publique du Québec, and Département de médecine sociale et préventive, Faculté de médecine, Université Laval, Québec City, Québec G1V 5B3, Canada. Electronic address: celine.campagna@inspq.qc.ca.
Céline
C
Campagna
Département de santé environnementale et santé au travail, École de santé publique, Université de Montréal, Montréal, Québec H3T 1J4, Canada. Electronic address: robert.tardif@umontreal.ca.
Robert
R
Tardif
Département de médecine sociale et préventive, Faculté de médecine, Université Laval and Axe de recherche neurosciences cliniques et cognitives, Institut universitaire en santé mentale de Québec, Centre intégré de santé et de services sociaux de la Capitale-Nationale, Québec City, Québec G1V 0A6, Canada. Electronic address: alexandre.bureau@msp.ulaval.ca.
Alexandre
A
Bureau
D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System; D004202:Disinfectants / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D018811:Maternal Exposure; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D022882:Trihalomethanes
D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System; D004202:Disinfectants; D005982:Glutathione Transferase; D022882:Trihalomethanes; C413545:glutathione S-transferase T1
CYP2E1; DBPs; GSTM1; GSTT1; Gene polymorphisms; Intra-uterine-growth-restriction