Association between <i>IRF6</i> SNPs and Oral Clefts in West China

Huang, Ying; Wu, Jue; Ma, Juan; Beaty, Terri H.; Sull, Jae Woong; Zhu, Lucheng; Lu, Daru; Wang, Y.; Meng, Tong; Shi, Bing

doi:10.1177/0022034509341040

Cited by 55 publications

(49 citation statements)

References 14 publications

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“…The SNP rs2235371 (V274I) was the first marker in IRF6 shown to be associated with NSCL/P, notably in Asian and South American populations [Zucchero et al, 2004]. This association was further reproduced in other populations, including those of European descent, and with other IRF6 SNPs in linkage disequilibrium (LD) with V274I [Park et al, 2007;Jugessur et al, 2008;Huang et al, 2009;Blanton et al, 2010]. A second SNP, rs642961 (G>A), located in an IRF6 enhancer, was reported as a likely cause of the association between the previously tested IRF6 SNPs and NSCL/P and a more pronounced effect was observed in cleft lip only (CPO) patients than in cleft lip with cleft palate (CLP) patients.…”

Section: Introductionmentioning

confidence: 90%

IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population

Brito

Bassi

Masotti

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 a complex disorder with a worldwide incidence estimated at 1:700. Among the putative susceptibility loci, the IRF6 gene and a region at 8q24.21 have been corroborated in different populations. To test the role of IRF6 in NSCL/P predisposition in the Brazilian population, we conducted a structured association study with the SNPs rs642961 and rs590223, respectively, located at 5' and 3' of the IRF6 gene and not in strong linkage disequilibrium (LD), in patients from five different Brazilian locations. We also evaluated the effect of these SNPs in IRF6 expression in mesenchymal stem cells (MSC). We observed association between rs642961 and cleft lip only (CLO) (P=0.009; odds ratio (OR) for AA genotype=1.83 [95% Confidence interval (CI), 0.64-5.31]; OR for AG genotype=1.72 [95% CI, 1.03-2.84]). This association seems to be driven by the affected patients from Barbalha, a location which presents the highest heritability estimate (H2=0.85), and the A allele at rs642961 is acting through a dominant model. No association was detected for the SNP rs590223. We did not find any correlation between expression levels and genotypes of the two loci, and it is possible that these SNPs have a functional role in some specific period of embryogenesis.

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Section: Introductionmentioning

confidence: 90%

IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population

Brito

Bassi

Masotti

et al. 2012

American J of Med Genetics Pt A

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“…Zucchero et al [2004] collected a large dataset consisting of nearly 2,000 NSOC families from Asia, Europe, North and South America, and found variants in the IRF6 gene were associated with risk of NSOC in multiple populations. From then on, replication studies from different populations and ethnic groups have been performed, including Italian, European-American, Belgian, Taiwanese, Singaporean, Korean, and Chinese populations [Zucchero et al, 2004;Blanton et al, 2005;Ghassibe et al, 2005;Scapoli et al, 2005;Srichomthong et al, 2005;Park et al, 2007;Jugessur et al, 2008;Huang et al, 2009]. Notably, one SNP (rs2235371, C > T), altering the conserved amino acid valine to isoleucine at codon 274 in the SMIR-binding domain (SMAD-IRF-binding domain), was significantly associated with NSOC, especially in Asians and South Americans [Park et al, 2007].…”

Section: Introductionmentioning

confidence: 99%

IRF6 polymorphisms are associated with nonsyndromic orofacial clefts in a Chinese Han population

Pan

Zhang

et al. 2010

American J of Med Genetics Pt A

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IRF6 plays an important role in orofacial development. In the present study, we genotyped two polymorphisms (rs642961 and rs2235371) within the IRF6 locus and estimated their associations with risk of nonsyndromic orofacial clefts (NSOC), including the subgroups, in a hospital-based case-control study in a Chinese Han population. In the single locus analyses, we found rs642961 AG and AG/AA genotypes were associated with increased risk of NSOC, especially cleft lip with or without cleft palate (CL/P) and cleft lip with cleft palate (CLP), while significantly decreased risks were associated with rs2235371 CT and CT/TT genotypes. When examining the combined effects of these two polymorphisms and using the rs642961 A and rs2235371 C alleles as the risk alleles, we found genotypes containing 2-4 risk alleles conferred high risk to NSOC, CL/P, and CLP. Furthermore, to test whether rs642961 could modulate IRF6 expression in vivo, we surgically collected lip skin tissues within the adjacent region of lip cleft site and found rs642961 genotypes were associated with differential levels of IRF6 mRNA and protein expression in an allele-dosage manner, providing the first evidence that rs642961 affected IRF6 expression in vivo. Taken together, these findings confirm the contribution of IRF6 genetic variants in the etiology of NSOC in a Chinese Han population.

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“…This site is located in the SMIR domain and is commonly seen in 3% of healthy European and 22% of healthy Asian populations [1]. In addition, this mutation has been shown to be associated with NSCL/P in a western Chinese population [18,19]. We speculate that this missense mutation is probably related to nonsyndromic CL/P in Guangdong Province.…”

Section: Irf6 Gene Sequences and Snp Characteristicsmentioning

confidence: 83%

Presence of sequence and SNP variation in the IRF6 gene in healthy residents of Guangdong Province

Hua

Wang

et al. 2016

Open Life Sciences

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ObjectiveThis study was to investigate the single nucleotide polymorphism (SNP) in the interferon regulatory factor 6 (IRF6) gene in healthy residents of Guangdong Province, China, for further analysis of their associations with the development of cleft lip with or without palate (CL/P).MethodologyDNA was extracted from blood samples of 13 healthy residents. IRF6 genes were sequenced and analyzed by alignment to the reference sequences in GenBank.ResultsThe IRF6 genes containing 45.21% GC were 25016–25046 bp in length, and had 2215-bp exons and a 1404-bp coding region. There were 65 SNPs, including 58 SNPs in the 5′-untranslated region or introns and 7 SNPs in the exons. These sites had two alleles, including 39 transition sites and 26 transversion sites. Five novel SNPs were identified. c. 459G>T and c. 820G>A in the coding region represented silent and Val274Ile mutations, respectively. The SNPs made two sequences (GenBank HQ875393 and JF346417).ConclusionsThe sequences and SNP profiles of the IRF6 gene in healthy residents of Guangdong Province are consistent with the one in GenBank but with slight variations. Our findings form a basis for further investigation of the association between IRF6 gene polymorphisms and CL/P in residents of Guangdong Province.

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Association between IRF6 SNPs and Oral Clefts in West China

Cited by 55 publications

References 14 publications

IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population

IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population

IRF6 polymorphisms are associated with nonsyndromic orofacial clefts in a Chinese Han population

Presence of sequence and SNP variation in the IRF6 gene in healthy residents of Guangdong Province

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