Transforming Growth Factor-α and Nonsyndromic Cleft Lip with or without Palate in Brazilian Patients: Results of a Large Case-Control Study

Passos‐Bueno, Maria Rita; Gaspar, D. A.; Kamiya, Tânia; Tescarollo, Graziela; Rabanéa, Daniel; Richieri-Costa, Antônio; Alonso, Nivaldo; Araujo, B. C.

doi:10.1597/03-054.1

Cited by 16 publications

(14 citation statements)

References 26 publications

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“…1 In this study, the C2 allele frequency was 0.06, similar to that reported in previous case-control studies performed in Brazil. 15,16 Several studies (case-control and case-parent triads) found an association between a TGFA / Taq I polymorphism and clefting; 10,12,17,18 however, other studies did not find an association. [19][20][21][22] We did not find any evidence of association between TGFA / Taq I polymorphisms and oral cleft in the population studied.…”

Section: Discussionmentioning

confidence: 99%

TGFA/Taq I polymorphism and environmental factors in non-syndromic oral clefts in Southern Brazil

et al. 2012

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We report a study of TGFA / Taq I polymorphisms and environmental factors in non-syndromic oral cleft in Southern Brazil. Nonsyndromic cleft case-parent triads were recruited to participate. Clinical data was collected with an emphasis on tobacco and alcohol use during pregnancy. DNA was extracted from peripheral blood and TGFA / Taq I polymorphisms were analyzed by PCR / RFLP with Taq I restriction enzyme. Association of clefts and TGFA / Taq I polymorphisms was determined using a transmission disequilibrium test (TDT). Association of environmental factors, clefts, and genotypes was evaluated with Fisher's exact test. The minor allele frequency was 0.064. We found no evidence of association between TGFA / Taq I polymorphisms and clefting (TDT p = 0.335). We also found no association between TGFA / Taq I polymorphisms and environmental factors (alcohol and/or tobacco). Therefore, no evidence was found that TGFA / Taq I polymorphisms play a role in clefting in this population. No evidence was found that tobacco or alcohol exposure during pregnancy was related to clefting, however a larger sample size is needed to confirm these results.

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Section: Discussionmentioning

confidence: 99%

TGFA/Taq I polymorphism and environmental factors in non-syndromic oral clefts in Southern Brazil

et al. 2012

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“…Some of the BCL3 and TGFA data have already been included in previous reports. 20,22 Gene -gene interactions were tested using a two-step approach. First, we applied a linkage disequilibrium test to verify if a combination of alleles at two different loci is preferentially present in the considered sample.…”

Section: Discussionmentioning

confidence: 99%

“…These findings were replicated in some studies, but there have been a growing number of reports not confirming this association (revised in). 4,22 Considering that deficiency of folate would cause an impairment on cell proliferation or migration during embryogenesis, we hypothesized that the presence of a maternal CT or TT/ MTHFR genotype together with the embryo C1C2/TGFA or C2C2/TGFA genotypes may favor the occurrence of CL/P. We did not observe any interaction between maternal MTHFR and TGFA offspring genotypes.…”

Section: Gene -Gene Interactionsmentioning

confidence: 92%

Maternal MTHFR interacts with the offspring's BCL3 genotypes, but not with TGFA, in increasing risk to nonsyndromic cleft lip with or without cleft palate

et al. 2004

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The 677 C-T polymorphism in the 5-10 methylenetetrahydrofolate reductase (MTHFR) gene has been associated with nonsyndromic cleft lip with or without cleft palate (CL/P) in some populations, but not others. Previous studies (ie, case-control and transmission disequilibrium tests (TDT)) in Brazilian families with CL/P have been unable to replicate this putative association. However, our group observed a lower proportion of CT heterozygotes among the mothers of CL/P probands, suggesting that the maternal genotype for this polymorphism might influence predisposition to CL/P. In order to further examine this issue, we performed a case-control study of the 677 C-T/MTHFR polymorphism in families with CL/P ascertained in two regions of Brazil: 172 from São Paulo (SP) and 252 from Ceará (CE). The control samples included 243 individuals from SP and 401 from CE. TDT was carried out in 102 patients with CL/P and their parents. No evidence of an association was observed between the 677 C-T/MTHFR polymorphism and CL/P using the case-control design, while borderline significance was obtained with the TDT (P ¼ 0.055). We have also looked for an interaction between maternal MTHFR genotypes and the propositi offspring's genotypes at two candidate susceptibility loci for CL/P, TGFA and BCL3. Interestingly, we observed an interaction between the maternal MTHFR and offspring's BCL3 genotypes (OR: 2.3; 95% CI: 1.1 -4.8; P ¼ 0.03) but not with the offspring's TGFA genotypes. Therefore, our results reinforce the idea that the maternal MTHFR genotype plays a significant role in susceptibility to CL/P, but its teratogenic effect depends on the genotype of the offspring.

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“…However, other studies have not been able to replicate this finding by either linkage or association [9,17,18]. Two meta-analyses, one looking at association studies [19] and a more recent study combining 13 genome scan studies [20•], reveal positive results, corroborating the hypothesis that TGFA is a modifier rather than necessary or sufficient to cause clefting.…”

Section: P13 (Tgfa)mentioning

confidence: 99%

Progress toward discerning the genetics of cleft lip

Lidral

Moreno

2005

Current Opinion in Pediatrics

111

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Purpose of review-Orofacial clefts are common birth defects with a known genetic component to their etiology. Most orofacial clefts are nonsyndromic, isolated defects, which can be separated into two different phenotypes: (1) cleft lip with or without cleft palate and (2) cleft palate only. Both are genetically complex traits, which has limited the ability to identify disease loci or genes. The purpose of this review is to summarize recent progress of human genetic studies in identifying causal genes for isolated or nonsyndromic cleft lip with or without cleft palate.Recent findings-The results of multiple genome scans and a subsequent meta-analysis have significantly advanced our knowledge by revealing novel loci. Furthermore, candidate gene approaches have identified important roles for IRF6 and MSX1. To date, causal mutations with a known functional effect have not yet been described.Summary-With the implementation of genome-wide association studies and inexpensive sequencing, future studies will identify disease genes and characterize both gene-environment and gene-gene interactions to provide knowledge for risk counseling and the development of preventive therapies.

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Transforming Growth Factor-α and Nonsyndromic Cleft Lip with or without Palate in Brazilian Patients: Results of a Large Case-Control Study

Abstract: These data further suggest that TGFA is not a relevant modifier locus for the occurrence of CL/P.

Cited by 16 publications

References 26 publications

TGFA/Taq I polymorphism and environmental factors in non-syndromic oral clefts in Southern Brazil

TGFA/Taq I polymorphism and environmental factors in non-syndromic oral clefts in Southern Brazil

Maternal MTHFR interacts with the offspring's BCL3 genotypes, but not with TGFA, in increasing risk to nonsyndromic cleft lip with or without cleft palate

Progress toward discerning the genetics of cleft lip

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