American Journal of Epidemiology Advance Access originally published online on September 28, 2005
American Journal of Epidemiology 2005 162(9):891-897; doi:10.1093/aje/kwi293
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original Contribution |
Parent-of-Origin Transmission of Thrombophilic Alleles to Intrauterine Growth-Restricted Newborns and Transmission-Ratio Distortion in Unaffected Newborns
1 Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montréal, Québec, Canada
2 Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC
Correspondence to Dr. Claire Infante-Rivard, Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, 1130 Pine Avenue West, Montréal, Québec, Canada H3A 1A3 (e-mail: claire.infante-rivard{at}mcgill.ca).
Findings on the role of thrombophilic polymorphisms in adverse pregnancy outcomes, particularly intrauterine growth restriction, are inconsistent. Such inconsistencies may be partly due to two types of effects which have not been considered before with regard to thrombophilic genes: parent-of-origin effects (imprinting) and transmission-ratio distortion effects (allele transmission differing from that expected in unaffected subjects). In this study of infants born at a Canadian hospital (1998–2000), the authors investigated both types of effects. Cases (n = 493) were defined as newborns whose birth weight for gestational age and sex was below the 10th percentile by national standards, and controls (n = 472) as newborns at or above the 10th percentile. Log-linear models were used to analyze the transmission of variant alleles among case- and control-parent trios. A single copy of a common polymorphism, Val34Leu in factor XIII, increased the risk of intrauterine growth restriction approximately 70% when the parent of origin was the father as opposed to the mother (p < 0.05). Among unaffected newborns, transmission of A1298C in the methylenetetrahydrofolate reductase gene (p < 0.005), transmission of the G1691A variant in factor V Leiden (p < 0.002), and transmission of the G20210A variant in the prothrombin (factor II) gene (p < 0.001) occurred significantly less often than expected (transmission-ratio distortion). Affected newborns also inherited the prothrombin G20210A variant significantly less often than expected. These results suggest that these three genes exhibit segregation distortion or reduce gestational survival.
alleles; factor XIII; fetal development; fetal growth retardation; genomic imprinting; polymorphism, genetic; thrombophilia
Abbreviations: LL-LRT, log-linear likelihood ratio test; MTHFR, methylenetetrahydrofolate reductase; PAI-1, plasminogen activator inhibitor-1; PO-LRT, parent-of-origin likelihood ratio test
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Bochud, A. Chiolero, R. C Elston, and F. Paccaud A cautionary note on the use of Mendelian randomization to infer causation in observational epidemiology Int. J. Epidemiol., April 1, 2008; 37(2): 414 - 416. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Beaty Invited Commentary: Two Studies of Genetic Control of Birth Weight Where Large Data Sets Were Available Am. J. Epidemiol., April 1, 2007; 165(7): 753 - 755. [Abstract] [Full Text] [PDF]
|
|