{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T03:13:53Z","timestamp":1770434033818,"version":"3.49.0"},"reference-count":39,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2007,8,28]],"date-time":"2007-08-28T00:00:00Z","timestamp":1188259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Idiopathic talipes equinovarus (ITEV), or isolated clubfoot, is a common developmental anomaly that is characterized by a rigid foot, adducted forefoot, cavus midfoot, equinovarus of the hindfoot, and hypoplastic calf musculature. The etiology of this common birth defect is largely unknown, but genetic factors have been implicated in population and family studies and maternal smoking during pregnancy has been identified as an environmental risk factor. The biotransformation of exogenous substances, such as tobacco smoke, is modulated by numerous genes including<jats:italic>N<\/jats:italic>\u2010acetylation genes,<jats:italic>NAT1<\/jats:italic>and<jats:italic>NAT2<\/jats:italic>. Functional variants of these genes exist and can be distinguished by genotyping. We hypothesized that variation in<jats:italic>NAT1<\/jats:italic>and<jats:italic>NAT2<\/jats:italic>genes might be associated with ITEV. To test this hypothesis,<jats:italic>NAT1<\/jats:italic>and<jats:italic>NAT2<\/jats:italic>were genotyped in a sample of 56 multiplex ITEV families, 57 trios with a positive family history and 160 simplex trios with ITEV. The results detected a slight decrease in the expected number of homozygotes for the<jats:italic>NAT2<\/jats:italic>normal allele in the Hispanic simplex trios. In addition, in a pilot case\u2013control study of ITEV, there were significantly more slow<jats:italic>NAT2<\/jats:italic>acetylators among the cases. This suggests that slow acetylation may be a risk factor for ITEV. This study is the first to find evidence suggesting a role for a biotransformation candidate gene in the etiology of ITEV and provides a scientific foundation to further explore the contributions of other tobacco metabolism genes in the etiology of clubfoot. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.31927","type":"journal-article","created":{"date-parts":[[2007,8,28]],"date-time":"2007-08-28T18:46:42Z","timestamp":1188326802000},"page":"2285-2291","source":"Crossref","is-referenced-by-count":30,"title":["<i>NAT2<\/i>variation and idiopathic talipes equinovarus (clubfoot)"],"prefix":"10.1002","volume":"143A","author":[{"given":"Jacqueline 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