Disinfection by-products exposure and intra-uterine growth restriction: Do genetic polymorphisms of CYP2E1or deletion of GSTM1 or GSTT1 modify the association?

Abstract

Background-Exposure to disinfection by-products (DBPs) during pregnancy was associated with reduced fetal 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 geneenvironment interactions and their results were never replicated.Objective-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.Methods-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.Results-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. Conclusions-Previous positive interactions betweenTHMs exposure and CYP2E1 and GSTM1 were not replicated but interactions with other CYP2E1 polymorphisms are reported.

Impact of chloroform exposures on reproductive and developmental outcomes: A systematic review of the scientific literature

“…Twenty‐five had been reviewed previously by OEHHA (). There were five studies not included in the OEHHA review (Brender et al, ; Cao et al, ; Kogevinas et al, ; Levallois et al, ; Wright et al, ). Eleven studies were prospective cohort studies, 11 studies were retrospective cohort studies, and 8 were case–control studies (7 population‐based and 1 hospital‐based case–control study).…”

“…One of the major methodological shortcomings of many of the studies included in this evaluation is the lack of adequate exposure assessment. Only 13 (Botton et al, ; Cao et al, ; Costet et al, ; Danileviciute et al, ; Grazuleviciene et al, ; Grazuleviciene et al, ; Iszatt et al, ; Kogevinas et al, ; Levallois et al, ; Levallois et al, ; Savitz et al, ; Smith et al, ; Villanueva et al, ) of the 30 studies assessed in this review incorporated individual‐level exposure information (e.g., frequency and duration of showering, use of a water filter, and bottled versus tap water consumption) when estimating a mother's exposure to chloroform during pregnancy; the other 17 studies relied solely on chloroform sampling data in local or regional water, and in one case, in air (Brender et al, ), for chloroform exposure estimation. Thus, these studies were semi‐ecologic in nature, meaning that they relied on group‐level geographic exposure data.…”

“…Because exposure assessment is so fundamental to the validity of epidemiologic research, we classified study quality based largely on whether exposure assessment was integrated using individualized data. That is, we classified the studies with integrated exposure estimates as being relatively strong methodologically (Botton et al, ; Cao et al, ; Costet et al, ; Danileviciute et al, ; Grazuleviciene et al, ; Grazuleviciene et al, ; Iszatt et al, ; Kogevinas et al, ; Levallois et al, ; Levallois et al, ; Savitz et al, ; Smith et al, ; Villanueva et al, ) compared with studies that lacked integrated exposure estimates (Brender et al, ; Dodds & King, ; Hinckley et al, ; Hoffman et al, ; Infante‐Rivard, ; Iszatt et al, ; Kramer et al, ; Lewis et al, ; Lewis et al, ; Porter, PutnaD, Hunting, & Riddle, ; Rivera‐Núñez & Wright, ; Summerhayes et al, ; Toledano et al, ; Wennborg et al, ; Wright et al, ; Wright et al, ; Zhou et al, ). While exposure assessment is one of many aspects that influence the quality of any study, given the critical importance of exposure assessment in this subject matter, we determined that the use of an integrated (i.e., individualized) exposure assessment method should be required of any study to be considered informative on the potential causal relationship between chloroform exposure and developmental outcomes (Koepsell & Weiss, ; Morgenstern, ).…”

“…These studies represent 13 separate populations, with 43 associations estimated across different levels and periods of exposure. Thirteen of the 17 studies (37 associations) observed no clear increased or decreased risk of small for gestational age infants with increasing chloroform exposure (Cao et al, ; Costet et al, ; Danileviciute et al, ; Grazuleviciene et al, ; Hinckley et al, ; Hoffman et al, ; Infante‐Rivard, ; Kogevinas et al, ; Levallois et al, ; Levallois et al, ; Rivera‐Núñez & Wright, ; Savitz et al, ; Villanueva et al, 2011). The other four studies (six associations) found a significant increase in risk of small for gestational age with increased exposure to chloroform during pregnancy (Kramer et al, ; Porter et al, ; Summerhayes et al, ; Wright et al, ).…”

“…Not a single study of small for gestational age that used an integrated approach for assessing chloroform exposure (of which there were nine) found a statistically significant association between chloroform exposure and risk of small for gestational age (Cao et al, ; Costet et al, ; Danileviciute et al, ; Grazuleviciene et al, ; Kogevinas et al, ; Levallois et al, ; Levallois et al, ; Savitz et al, ; Villanueva et al, 2011). In the absence of significant associations among studies with methodologically rigorous chloroform exposure assessment, combined with the inconsistency of observed associations across all available studies, the preponderance of the evidence does not establish a clear association between chloroform exposure during pregnancy and small for gestational age infants.…”