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Risks of human limb deficiency anomalies associated with 29 SNPs of genes involved in homocysteine metabolism, coagulation, cell–cell interactions, inflammatory response, and blood pressure regulation
Author(s) -
Carmichael Suzan L.,
Shaw Gary M.,
Iovannisci David M.,
Yang Wei,
Finnell Richard H.,
Cheng Suzanne,
Lammer Edward J.
Publication year - 2006
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.31505
Subject(s) - single nucleotide polymorphism , biology , genetics , loss of heterozygosity , odds ratio , population , medicine , genotype , homocysteine , endocrinology , gene , allele , environmental health
This study explored risks of limb deficiency anomalies associated with 29 single nucleotide polymorphisms (SNPs) of genes involved in homocysteine metabolism, coagulation, cell–cell interaction, inflammatory response, and blood pressure regulation. The authors genotyped 96 cases and 437 non‐malformed controls from a California population‐based case‐control study (1987–1988 birth cohort). Increased risk of limb anomaly was observed for three SNPs: heterozygosity for F5 Arg506Gln, with an odds ratio (OR) of 2.5 (95% confidence interval (CI), 1.0, 6.5); heterozygosity for TNF (−376)G > A, OR 2.1 (0.7, 6.2); and homozygosity for NPPA 2238T > C, OR 4.0 (1.1, 15.4). We hypothesized that effects of variant genotypes in the presence of maternal smoking, and/or in the absence of supplement intake, may exceed effects of any of these factors alone. In particular, findings for polymorphisms in SERPINE1 , ITGA2 , SELE , TNF , LTA , NPPA , GNB3 , and ADRB2 supported the hypotheses, both for smoking and for supplement intake. These results suggest involvement of genetic variation of biologically relevant candidate genes, and gene–environment interaction, for some limb anomalies whose pathogenesis may be related to altered vascular tone or integrity. © 2006 Wiley‐Liss, Inc.