RESUMEN
BACKGROUND: Non-syndromic orofacial clefts (NSOC) is one of the most common congenital malformations, and its etiology involves both genetic and environmental factors. The present aimed to investigate the association of six single nucleotide polymorphisms (SNPs) (rs10512248 in PTCH1, rs12681366 and rs958447 in RAD54B, rs13317 in FGFR1, rs1838105 and rs4968247 in WNT9B) with NSOC in a Northern Chinese population. METHODS: In the present study, HI-SNP technology was used to conduct genotyping of the six SNPs (rs10512248, rs12681366, rs957448, rs13317, rs1838105 and rs4968247) in 596 patients with NSOC and 466 healthy individuals from a Northern Chinese population. RESULTS: The results obtained indicated that rs10512248 and rs12681366 minor allele frequencies were statistically significant (p = 0.020 and 0.015, respectively). Statistical analysis confirmed that the CT genotype of RAD54B rs12681366 was associated with a decreased risk of NSOC (odds ratio = 0.62, 95% confidence interval = 0.46-0.82, P = 0.001). After correcting for multiple testing, the associations remained significant. By contrast, nonsignificant differences were found for the rs957448, rs13317, rs1838105 and rs4968247 allele and genotype frequencies between cases and controls. CONCLUSIONS: These results demonstrate that the PTCH1 rs10512248 and RAD54B rs12681366 were significantly associated with NSOC in a Northern Chinese population. Additionally, the RAD54B rs12381366 CT genotype could decrease the risk of NSOC in a Northern Chinese population. We provide novel evidence for the development of NSOC in a Northern Chinese population.
Asunto(s)
Labio Leporino/genética , Fisura del Paladar/genética , ADN Helicasas/genética , Predisposición Genética a la Enfermedad/genética , Proteínas Nucleares/genética , Receptor Patched-1/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Pueblo Asiatico/genética , Niño , Preescolar , China , Labio Leporino/etnología , Fisura del Paladar/etnología , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/etnología , Genotipo , Haplotipos , Humanos , Lactante , Adulto JovenRESUMEN
BACKGROUND: The role of underlying genetic factors in the pathogenesis of nonsyndromic orofacial clefts (NSOC) remains poorly understood. Although genomewide association studies (GWASs) of NSOC have successfully identified a large number of novel genetic risk loci, association results of replication studies are inconsistent across different populations. METHODS: Six single nucleotide polymorphisms (SNPs) (rs7922405 at 10q26.3, rs73039426 at 19q13.11, rs7552 at 2p24.2, rs1788160 at 8q22.2, rs9381107 at 6p24.3, and rs17095681 at 10q25.3) were analyzed for an association with NSOC in 1062 participants of Chinese descent (596 patients and 466 controls). We applied the multifactor dimensionality reduction (MDR) method to detect potential gene-gene (G × G) interactions in the six SNPs. RESULTS: The genotype or allele frequencies of SNPs rs7922405, rs73039426, and rs7552 showed significant differences between the controls and patients with NSOC, whereas no association was shown between three SNPs (rs1788160, rs17095681, and rs9381107) and NSOC. MDR analysis did not reveal significant G × G interactions for susceptibility to NSOC. CONCLUSION: We confirmed that three genes (rs7922405 of MGMT, rs73039426 of RHPN2, and rs7552 of FAM49A) may contribute to NSOC in Chinese populations. MGMT and RHPN2 are associated with NSOC, which is herein demonstrated for the first time.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Encéfalo/anomalías , Labio Leporino/genética , Fisura del Paladar/genética , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Estudio de Asociación del Genoma Completo/métodos , Péptidos y Proteínas de Señalización Intracelular/genética , Polimorfismo de Nucleótido Simple/genética , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genética , Pueblo Asiatico/genética , Epistasis Genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , MasculinoRESUMEN
BACKGROUND: Nonsyndromic orofacial clefts (NSOC) are the most common orofacial congenital defect with a complex etiology. Genome-wide association studies have identified paired box protein 7 (PAX7) and netrin-1 (NTN1) as candidate susceptibility genes for NSOC in both European and Asian populations. Here, possible associations between single-nucleotide polymorphisms (SNPs) in or near PAX7 and NTN1 were investigated in relation to risk of NSOC in a northern Chinese population. METHODS: A total of 602 individuals with NSOC and 510 controls were recruited from northern China. Polymerase chain reaction-ligation detection reactions were used to analyze 4 SNPs (rs742071, rs6659735, rs766325, and rs4920520) of PAX7 and 2 SNPs (rs9904526 and rs9788972) of NTN1. Investigations of polymorphisms and risk of NSOC were conducted by using the PLINK software. RESULTS: NTN1 rs9788972 AG was found to be associated with an increased risk of NSOC compared to the GG homozygous genotype (ORâ=â1.43, 95% CIâ=â1.11-1.86, Pâ=â.006). When the multifactor dimensionality reduction method was applied, NTN1 rs9788972 still exhibited an increased risk for NSOC (Pâ=â.008). In contrast, SNPs in PAX7 were not associated with any increased risk of NSOC. CONCLUSION: NTN1 rs9788972 is identified as a risk locus for NSOC susceptibility in a northern Chinese population.
Asunto(s)
Encéfalo/anomalías , Labio Leporino/genética , Fisura del Paladar/genética , Predisposición Genética a la Enfermedad , Factores de Crecimiento Nervioso/genética , Factor de Transcripción PAX7/genética , Polimorfismo de Nucleótido Simple , Proteínas Supresoras de Tumor/genética , Pueblo Asiatico/genética , China , Labio Leporino/etnología , Fisura del Paladar/etnología , Femenino , Estudio de Asociación del Genoma Completo , Técnicas de Genotipaje , Humanos , Desequilibrio de Ligamiento , Masculino , Netrina-1 , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common craniofacial birth defects, and the etiology of NSCL/P involves both genetic and environmental factors. Genome-wide association study (GWAS) identified a novel susceptibility locus of ventral anterior homeobox 1 (VAX1) in patients with NSCL/P. However, the association of single nucleotide polymorphisms (SNPs) of VAX1 with NSCL/P is inconclusive due to the differences in the racial and ethnic populations. The aim of this study was to replicate the association between VAX1 and NSCL/P in a northern Chinese Han population. METHODS: Our study included 186 patients with NSCL/P and 223 healthy individuals from northern China. Five SNPs (rs4752028, rs10787760, rs7078160, rs6585429, and rs1871345) on VAX1 were genotyped using the SNaPshot method. RESULTS: Recessive genetic model analysis revealed that homozygous genotype CC of VAX1 rs4752028 was associated with an increased risk of NSCL/P (odds ratioâ=â1.89, 95% confidence intervalâ=â1.12-3.19, Pâ=â0.017), but the results were not significant after the Bonferroni correction for multiple comparisons. The allele and genotype frequencies of rs10787760, rs7078160, rs6585429, and rs1871345 and the allele frequencies of rs4752028 showed no significant differences between cases and controls. Haplotype and SNP-SNP interaction analyses did not detect any significant association of VAX1 with the occurrence of NSCL/P. CONCLUSION: VAX1 rs4752028 was weakly associated with NSCL/P development in the studied northern Chinese Han population.
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Encéfalo/anomalías , Labio Leporino/genética , Fisura del Paladar/genética , Proteínas de Homeodominio/genética , Factores de Transcripción/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Femenino , Humanos , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common congenital malformation with a worldwide prevalence rate of 0.4-2.0% among live births, depending on race and ethnic background. Single-nucleotide polymorphisms (SNPs) of genes may contribute to NSCLP risk, although the risk factors and pathogenesis of NSCLP remain unknown. The objective of this study was to investigate association of SNPs of noggin (NOG) and sprouty homolog 2 (SPRY2) with NSCLP risk. A total of 188 NSCLP patients and 228 healthy controls from northern China were recruited for genotyping of these SNPs using the SNaP shot method. The frequency of the NOG rs227731 genotype was significantly lower among NSCLP cases than among controls. Logistic regression analysis showed rs227731 CC genotype was associated with decreased NSCLP susceptibility (OR = 0.31, 95% CI = 0.12-0.80) compared to the AA homozygote. However, no association between SPRY2, SNPs, and NSCLP risk were observed in this cohort of patients. In conclusion, NOG rs227731 genotype was associated with decreased NSCLP risk in a Northern Chinese population.
Asunto(s)
Proteínas Portadoras/genética , Labio Leporino/genética , Fisura del Paladar/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Adulto , Alelos , Estudios de Casos y Controles , Niño , Preescolar , Labio Leporino/complicaciones , Fisura del Paladar/complicaciones , Femenino , Haplotipos , Humanos , Lactante , Masculino , Oportunidad Relativa , Adulto JovenRESUMEN
BACKGROUND: The p53 codon 72 polymorphism has been investigated extensively for its association with various cancers around the world. It is still unclear whether the p53 codon 72 polymorphism is associated with oral cancer risk. AIM: The aim of our study was to evaluate the association between the p53 codon 72 polymorphism and the oral cancer risk in Chinese Han patients. METHODS: A hospital-based case-control study with 200 patients with oral cancer and 200 matched controls was conducted. Genomic DNA was isolated from peripheral blood, and gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The arginine (Arg)/Arg genotype conferred 0.57 times reduced risk to oral cancer (95% confidence interval [CI]=0.36, 0.89; p=0.01). The Arg allele frequency was significantly lower (odds ratios [OR]=0.74, 95% CI=0.56, 0.98; p=0.03) in comparison with controls in patients with oral cancer. The proline allele frequency was significantly higher (OR=1.35, 95% CI=1.02, 1.79; p=0.03) in comparison with controls in patients with oral cancer. When stratified by the clinical stage, lymph node metastasis, and histological differentiation of oral cancer, no statistically significant results were observed. CONCLUSION: Our results thus suggest that the p53 codon 72 polymorphism modulates susceptibility to oral cancer in Chinese Han patients.
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Pueblo Asiatico/genética , Codón/genética , Genes p53/genética , Predisposición Genética a la Enfermedad , Neoplasias de la Boca/genética , Polimorfismo Genético/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Pueblo Asiatico/etnología , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
We present a rare case of recurrent aggressive fibromatosis of the maxilla in a 61-year-old woman, who was treated by resection of the left maxilla. Adjuvant treatments, particularly radiotherapy, are valuable if the tumour recurs.