Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Mesoamerican population: Evidence for <i>IRF6</i> and variants at 8q24 and 10q25

Rojas-Martínez, Augusto; Reutter, Heiko; Chacón‐Camacho, Oscar F.; León-Cachón, Rafael B. R.; Muñoz-Jiménez, Sergio G.; Nowak, Stefanie; Becker, Jéssica; Herberz, Ruth; Ludwig, Kerstin U.; Paredes-Zenteno, Mario; Arizpe-Cantú, Abelardo; Raeder, Susanne; Herms, Stefan; Ortíz-López, Rocío; Knapp, Michael; Hoffmann, Per; Nöthen, Markus M.; Mangold, Elisabeth

doi:10.1002/bdra.20689

Cited by 56 publications

(63 citation statements)

References 11 publications

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“…The most significant results, persisting after Bonferroni correction, were observed when the additive model was used, confirming dosage risk effect of minor allele A. Positive association between the IRF6 rs642961 variant and nsCL/P has been confirmed by multiple studies involving various ethnicities [21][22][23][24] . Also, our results are in accordance with the findings from two case-control studies on Central European populations which showed similar magnitudes of odds ratios 10,19 .…”

Section: Discussionmentioning

confidence: 58%

“…However, the subsequent replication studies conducted in the Mesoamerican, Italian, Chinese Han and Kenyan populations did not confirm these positive results 21,31,33,34 . The nucleotide variant rs227731 is located 100kb centromeric of the NOG gene.…”

Section: Discussionmentioning

confidence: 85%

“…SNP rs7078160 is intergenic, located near the VAX1 gene encoding a transcriptional regulator with a DNA-binding homeobox domain. An association between rs7078160 and nsCL/P has been replicated in several studies, which included European and Mesoamerican samples 20,21,37 , but Chinese and Kenyan studies 33,34 have reported contradictory results. A meta-analysis of 7 eligible studies 38 showed only a modest association of rs7078160 with nsCL/P risk.…”

Section: Discussionmentioning

confidence: 89%

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Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

Salagovic¹,

Klimčáková²,

Zabavnikova³

et al. 2017

BIOMED PAP

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Background. Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is the most common orofacial birth defect with an aetiology involving both genetic and environmental factors. Genome-wide association studies (GWAS) have identified several genomic susceptibility regions for nsCL/P. In the present study, the three well established single nucleotide polymorphisms (SNPs) identified by GWAS (rs987525 at 8q24, rs7078160 at 10q25, and rs227731 at 17q22 loci) and one SNP identified by candidate gene study (rs642961 in IRF6 gene at 1q32 locus) were analysed for an association with nsCL/P in Slovak population. Methods. Nucleotide variants were genotyped in 165 nsCL/P patients and 326 unaffected controls. All variants of interest were genotyped using high-resolution melting analysis after real-time PCR. Results. We found significant differences between patient and control groups with respect to the allele and genotype frequencies for the SNPs at the 1q32, 8q24, and 17q22 loci. SNP at the 10q25 locus showed a trend toward association with nsCL/P risk. Conclusions.The results suggest that SNPs at the 1q32, 8q24 and 17q22 loci may contribute to the nsCL/P risk in Slovak population.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 89%

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Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

Salagovic¹,

Klimčáková²,

Zabavnikova³

et al. 2017

BIOMED PAP

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“…The second one, by extending the initial German GWAS samples, identified two novel NSOC susceptibility loci (rs223371and rs7078160) and was then followed by three replication studies, where inconsistent results were presented. Specifically, rs7078160 rather than rs223371 was identified as a risk factor for NSOC in studies from Mesoamerican [Rojas-Martinez et al, 2010] and Estonian [Nikopensius et al, 2010] populations; however, neither was verified in a Chinese population [Pan et al, 2010b]. This lack of replication may be due to differences in genetic background between populations or it could reflect limited power due to small sample sizes.…”

Section: Discussionmentioning

confidence: 57%

“…The first one, performed in a German population, reported a novel susceptibility locus on chromosome 8q24.21 (rs987525) . Then, replication studies were conducted in three independent samples of European decents and successfully confirmed the role of SNPs in 8q24.21 in the development of NSOC Grant et al, 2009;Rojas-Martinez et al, 2010]. The second one, by extending the initial German GWAS samples, identified two novel NSOC susceptibility loci (rs223371and rs7078160) and was then followed by three replication studies, where inconsistent results were presented.…”

Section: Discussionmentioning

confidence: 94%

Different roles of two novel susceptibility loci for nonsyndromic orofacial clefts in a Chinese Han population.

Pan

Zhang

et al. 2011

American J of Med Genetics Pt A

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Nonsyndromic orofacial clefts (NSOC) are the most common developmental anomalies in human beings. Recently, a large-scale genome-wide association study identified two novel NSOC susceptibility loci: rs13041247 near MAFB and rs560426 near ABCA4. In the present study, we recruited 396 NSOC cases and 384 healthy controls to replicate their associations with risk of NSOC as well as their subgroups in a Chinese Han population. We found the overall genotype and allele frequencies of rs13041247, but not rs560426 were significantly different between cases and controls. Further logistic regression analysis showed rs13041247 CT, CC, and CT/CC were associated with decreased NSOC susceptibility, compared with rs13041247 TT wide-type homozygote. Moreover, the apparent protection against cleft lip with or without cleft palate (CL/P), cleft lip with cleft palate (CLP), and cleft lip only (CLO) was also identified in stratified analysis. However, none of any rs560426 genotypes or alleles was associated with risk of NSOC or their subgroups. Taken together, our findings confirmed the contribution of MAFB in the etiology of NSOC in a Chinese Han population.

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Three polymorphisms in IRF6 and 8q24 are associated with nonsyndromic cleft lip with or without cleft palate: Evidence from 20 studies

Wang

Pan

Zhang

et al. 2012

American J of Med Genetics Pt A

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Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common craniofacial malformation in humans. Three polymorphisms, rs2235371 and rs642961 in interferon regulatory factor 6 (IRF6), rs987525 on 8q24, have been shown to be associated with NSCL/P risk in several studies. However, the magnitudes of the association varied between studies. We therefore performed a meta-analysis to investigate this relationship. Two authors independently extracted information on the characteristics of the eligible studies. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Overall, 20 published case-control studies were included in the meta-analysis. We found that rs2235371 A allele had a significantly decreased risk (OR: 0.73, 95% CI: 0.61-0.88), whereas rs642961 A allele had a significantly increased risk of NSCL/P (OR: 1.44, 95% CI: 1.30-1.59), compared with the G allele. For 8q24 rs987525, the A allele was associated with a significantly increased risk of NSCL/P, compared with the C allele (OR: 1.71, 95% CI: 1.40-2.09). Furthermore, in the stratified analysis by ethnicity and types of NSCL/P, significant associations were still observed in the subgroups of ethnicity and types. Taken together, the results suggest that the IRF6 rs2235371, rs642961, and 8q24 rs987525 polymorphisms are associated with NSCL/P risk.

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Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Mesoamerican population: Evidence for IRF6 and variants at 8q24 and 10q25

Abstract: These results suggest that IRF6 and the 10q25 and 8q24 loci confer a risk for the development of NSCL/P in persons of Mayan origin.

Cited by 56 publications

References 11 publications

Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

Different roles of two novel susceptibility loci for nonsyndromic orofacial clefts in a Chinese Han population.

Three polymorphisms in IRF6 and 8q24 are associated with nonsyndromic cleft lip with or without cleft palate: Evidence from 20 studies

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