Maternal cigarette smoke exposure during pregnancy has been identified as a risk factor for adverse reproductive outcomes, a major public health concern. However, little is known about genetic susceptibility and possible interactions with environmental factors to increase risk of these events. This study was designed to investigate relative contributions of genetic and maternal environmental risk factor interactions to adverse reproductive outcomes. Maternal peripheral and umbilical cord blood samples from 1148 healthy mother/newborn pairs were genotyped for a panel of polymorphisms associated with the metabolic enzymes CYP1A1, CYP2E1, GSTM1, GSTT1 and NAT2* for several subgroups; low birthweight (<2500g, n=86), preterm delivery (<37th gestational week, n=93), premature birth (<2500g & <37th gestational week, n=53) and small for gestational age (SGA) at term (d37th gestational week, n=948) in comparison to the average for gestational age (AGA) group (n=948).
Maternal cigarette smoking during the last trimester was significantly associated with birthweight reduction (Ý=101.4g, SE=32, p=0.002). Maternal GSTT1 null genotype was significantly associated with low birthweight (OR=1.97, 95% CI: 1.24-3.12, p=0.004), preterm delivery (OR=1.91, 95% CI: 1.22-2.98, p=0.004) and premature birth (OR=2.42, 95% CI: 1.38-4.26, p=0.002). The mean reduction of birthweight observed among the maternal GSTT1 null genotype group was 89.6g (SE=37, p=0.018) and the mean reduction in gestational age was 0.25 weeks (SE=0.1, p=0.049). In addition, African American women were more likely to have a smaller baby; the mean reduction of birthweight was 230g (SE=34.5, p<0.001) compared with Caucasians. An additive interaction between smoking, African American ethnicity and GSTT1 null genotype was observed (OR=7.81, 95% CI: 2.49-24.43, p<0.001). The mean birthweight reduction observed in this group was 570.0g (SE=117, p<0.001) and the mean gestational age reduction was 1.10 weeks (SE=0.4, p=0.007). A similar risk was observed for newborn GSTT1 null genotype in the presence of maternal smoking (426.7g,SE=111, p<0.001) and (1.0 weeks, SE=0.4, p=0.012).
These results demonstrated a clear overrepresentation of maternal and newborn GSTT1 null genotype among adverse reproductive outcome cases. Furthermore, a gene-gene-environment interaction was observed where the combination of maternal and newborn GSTT1 null genotype in the presence of maternal cigarette smoke during pregnancy significantly increased risk of adverse reproductive outcomes.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-08142002-155319 |
| Date | 18 September 2002 |
| Creators | Nukui, Tomoko |
| Contributors | Marjorie Romkes, Ph.D., William L. Bigbee, Ph.D., Robert A. Branch, M.D., Billy W. Day, Ph.D., Phouthone Keohavong, Ph.D., Roberta B. Ness, M.D., M.P.H. |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu:80/ETD/available/etd-08142002-155319/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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