Abstract 1361 Poster Session IV, Tuesday, 5/4 (poster 259)

Introduction: Women differ considerably in their individual risks of delivering low birthweight infants; reasons for these differences are largely unknown. Humans are exposed to a variety of reproductive toxicants. Metabolism is essential to the detoxification of these toxicants. It is speculated that an individual's susceptibility to these toxicants may be modified by genetic variation in metabolic detoxification activities. Few studies have addressed genetic susceptibility in relation to birthweight, in particular, in the face of exposure to environmental toxicants.

Purpose: This study investigated association between maternal genetic polymorphisms of CYP1A1 (MspI and HincII) and the glutathione S-transferases (GSTM1 and GSTT1), genes involved in metabolism of organic xenobiotics, and infant birthweight, while adjusting for confounding variables.

Methods : The study was conducted in Yanshan District, Beijing, China. Beijing Yanshan Petrochemical Corporation (BYPC) is a major industry in the area. Eligible women consist of local residents who gave singleton live birth at BYPC hospital (A major hospital in the area) between June 1996 to June 1997. Response rate was about 92%. Epidemiologic data were obtained via interview using a questionnaire. A blood sample were obtained from each woman. Birth outcomes including birthweight and gestational age were recorded by trained nurse. Multiple linear regression was used to estimate the individual and the joint association between each polymorphism and birthweight. Women who smoked or drunk were excluded.

Results : A total of 304 singleton live born mother-infant pairs were included in the analysis. Both CYP1A1 MspI and HincII polymorphisms were significantly associated with reduced birthweight, -95 grams (se=48) and -132 grams (se=48), respectively, after adjusting for maternal age, education, parity, occupation, passive smoking, pre-pregnant weight and height, infant gestational age and sex. The analysis of the joint association showed that women with both MspI and HincII variant genotypes had a lower birthweight (-134 grams, se=53) than women with only MspI variant genotype (-13 grams, se=65). When studied alone, neither GSTM1 nor GSTT1 gene polymorphisms in mother were associated with infant birthweight. However, when CYP1A1 and GSTT1 polymorphisms were considered jointly, with homozygous wild type as reference, the reduction in birthweight was greatest among women with variant genotypes in both HincII and GSTT1 (-202 grams, se=93), much weaker for women with only variant genotypes in HincII (-108 grams, se=54), and none for women with only variant genotypes in GSTT1. Similar findings were obtained for the joint association of CYP1A1 MspI and GSTT1 polymorphisms with birthweight.

Conclusion: The association, as well as dose response nuture, support speculation regarding the importance of further assessing the role of genes and gene-environmental interactions in relation to birthweight.

Supported, in part, by the grant 20-FY98-0701 from the March of Dimes Birth Defects Foundation.