Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate

Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10-6<P<10-4) in a test for GxETS interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10-7 in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10-7 and P = 1.98×10-7 in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP. © 2014 Wu et al

Current data on the characterization of oral clefts in Brazil Informações atuais sobre a caracterização das fissuras orofaciais no Brasil

This study aimed at investigating the current distribution of the several types of clefts among the patients receiving treatment at the Hospital for Rehabilitation of Craniofacial Anomalies (HRAC-USP), Bauru, Brazil, for the first time during the year 2000. A total of 803 unoperated patients with cleft lip and/or palate, with or without additional malformations, with no recognizable syndromes, who came to the HRAC-USP for enrollment for treatment during the year 2000. A predominance of complete cleft lip and palate, either unilateral or bilateral, was observed (37.1%), followed by isolated cleft palate (31.7%) and isolated cleft lip (28.4%). A discrete relationship between cleft palate and the female gender was noticed (53%), and males were more affected by the other types of clefts (around 60%). The findings revealed a predominance of complete clefts of the primary and secondary palate, the treatment of which is more complex, and whose frequency is greater in males.<br>Foi objetivo do presente estudo investigar a distribuição atual dos vários tipos de fissuras entre pacientes que compareceram ao Hospital de Reabilitação de Anomalias Craniofaciais (HRAC-USP), Bauru, Brasil, pela primeira vez, no ano de 2000. No total, 803 pacientes não operados com fissura de lábio e/ou palato, com ou sem malformações adicionais, sem síndromes reconhecíveis, compareceram ao HRAC-USP para inscrição para tratamento durante o ano de 2000. Foi observada predominância de fissura completa de lábio e palato, unilateral ou bilateral (37,1%), seguida pela fissura de palato isolada (31,7%) e fissura de lábio isolada (28,4%). Foi notada uma relação discreta entre a fissura de palato e o gênero feminino (53%), sendo o gênero masculino mais afetado pelos outros tipos de fissuras (cerca de 60%). Os achados revelaram uma predominância de fissuras completas do palato primário e secundário, cujo tratamento é mais complexo, e uma maior ocorrência no gênero masculino