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ABSTRACT: Objective : To further confirm the association between two IRF6 single nucleotide polymorphisms and nonsyndromic cleft lip with or without cleft palate in a Chinese population. Participants : A total of 106 nonsyndromic cleft lip with or without cleft palate case trios and 129 control trios. Intervention : Two IRF6 single nucleotide polymorphisms, rs2235371 and rs642961, were genotyped for all case and control families. Case-control analysis and family-based linkage analysis were both performed for the two single nucleotide polymorphisms. Results : The genotype and allele frequencies of rs2235371 (odds ratioAG+AA vs. GG, 0.581; 95% confidence interval, 0.345 to 0.976; P = .039) and rs642961 (odds ratioAG+AA vs. GG, 5.389; 95% confidence interval, 2.936 to 9.893; P = 5e-08) were significantly higher in nonsyndromic cleft lip with or without cleft palate patients compared with controls. There was an obvious dosage effect of allele A at rs642961. The transmission of a major allele (G) of rs2235371 and a minor allele (A) of rs642961 was in disequilibrium (P < .05) in complete case-parent trios. The association between the two single nucleotide polymorphisms and nonsyndromic cleft lip with or without cleft palate was confirmed by the Family-Based Association Test for rs642961 (P = .008), but there was no significance for rs2235371 (P = 0.057). Haplotype analysis found that rs2235371 G/rs642961 A haplotype increased the risk of nonsyndromic cleft lip with or without cleft palate (P = 2.42e-07); whereas, rs2235371 A/rs642961 G haplotype reduced the risk of nonsyndromic cleft lip with or without cleft palate (P = 4.37e-05). No evidence of linkage disequilibrium was found between the two single nucleotide polymorphisms (D' = 0.303, r(2) = 0.017). Conclusion : Our results confirmed the involvement of the IRF6 variants rs642961 and rs2235371 in the etiology of nonsyndromic cleft lip with or without cleft palate in a Chinese population.
The Cleft Palate-Craniofacial Journal 03/2013; · 0.82 Impact Factor
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ABSTRACT: To assess the association between polymorphism of interferon regulatory factor 6 (IRF6) gene rs2235371 locus and nonsyndromic cleft lip with or without cleft palate in Chinese population.
Blood samples from 106 patients and their parents and 129 controls and their parents were collected. The polymorphism of IRF6 rs2235371 locus was determined with PCR-restriction fragment length polymorphism (PCR-RFLP) method. Case-control analysis, transmission disequilibrium test(TDT), haplotype-based haplotype relative risk analysis (HHRR) and family-based association test (FBAT) were carried out.
By case-control analysis, no significant difference was found in the frequencies of GG, GA and AA genotypes of rs2235371 locus between the patient group and control group (P> 0.05), but there was a significant difference in allelic frequencies (P< 0.05). There was also a significant difference in genotype and gene frequencies of rs2235371 variant between family members from cleft lip only group and control group. However, in cleft lip with cleft palate group, no such difference was observed. TDT analysis suggested a linkage in the presence of disequilibrium (chi-square=5.56, P=0.024). Results of HHRR analysis (chi-square=5.115, P=0.024) and FBAT (Z=2.218, P=0.027) also indicated an association between IRF6 rs2235371 variant and the risk of NSCL with or without cleft palate.
Genetic polymorphism of IRF6 gene rs2235371 locus is associated with NSCL with or without cleft palate.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 04/2012; 29(2):149-54.
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ABSTRACT: To find chromosome region closely linked to nonsyndromic cleft lip with or without palates (NSCL±P) by genome-wide scan and linkage analysis for two multiplex families.
Whole-genome scan and fine genome scan were used to analyse multiplex families members, and parametric, nonparametric and interaction statistical analysis software to determine which chromosomal section was linked to the genetic disease.
Both parametric and nonparametric linkage scores increased by a big margin over the initial linkage scores on 1q32.2-41. Although parametric results were not significant, nonparametric linkage gave a strong evidence for a candidate region on chromosome 2p25.1-24.2. The multiplicative model gave the strongest evidence for interaction in 1q32.2-41 and 2p25.1-24.2.
Parametric and nonparametric linkage analyses for 2 NSCL±P multiplex families show that there may be candidate regions on chromosome 1q32.2-41 and 2p25.1-24.2.The two regions of 1q32.2-41 and 2p25.1-24.2 may contribute to NSCL±P risks with interaction.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 06/2011; 43(3):333-7.
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ABSTRACT: To identify the loci involved in nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Northern Chinese people in Shenyang by using genomewide and interaction linkage scan.
Two multiplex families in Shenyang from North China were ascertained through probands with NSCL/P. Blood of every member was drawn for DNA extraction and analysis. Genotypes were available for 382 autosomal short tandem repeat (STR) markers from the ABI Prism Linkage Mapping Set version 2.5. Linkage between markers and NSCL/P was assessed by 2-point parametric LOD scores, multipoint-heterogeneity parametric LOD scores (HLODs), and multipoint nonparametric linkage score (NPL).
The initial scan suggested linkage on Chromosomes 1, 2, and 15. In subsequent fine mapping, 1q32-q42 showed a maximum multipoint LOD score of 1.9(empirical P=0.013) and an NPL score of 2.35 (empirical P=0.053). For 2p24-p25, the multipoint NPL increased to 2.94 (empirical P=0.007). 2-locus interaction analysis obtained a maximum NPL score of 3.73 (P=0.00078) and a maximum LOD score of 3 for Chromosome 1 (at 221 cM) and Chromosome 2 (at 29 cM).
Both parametric and nonparametric linkage scores greatly increased over the initial linkage scores on 1q32-q42, suggesting a susceptibility locus in this region. Nonparametric linkage gave a strong evidence for a candidate region on chromosome 2p24-p25. The superiority of 2-locus linkage scores compared to single-locus scores gave additional evidence for linkage on 1q32-q42 and 2p24-p25, and suggested that certain genes in the two regions may contribute to NCSL/P risks with interaction.
Biomedical and Environmental Sciences 10/2010; 23(5):363-70. · 1.35 Impact Factor
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ABSTRACT: To explore the relationship between genetic polymorphisms of MTHFR C677T and nonsyndromic cleft lip with or without palate in Chinese population.
There were 97 NSCL/P case-parent triads that were selected as case group. At the same period, 104 healthy subjects were selected together with their biological parents as control group. For all the subjects the polymorphism of MTHFR C677T was examined by PCR-RFLP method.
There was no statistical difference in genotype and gene frequencies for MTHFR C677T variants among family members between case group and control group in the offspring, fathers and mothers. The odds ratio(OR) between heterozygotes (CT) versus wild homozygotes (CC) were 1.02 (95% CI 0.47-2.21), 0.62 (95% CI 0.29-1.32) and 0.66 (95% CI 0.31-1.40) in the offspring, fathers and mothers, respectively. The OR between mutant homozygotes(TT) versus wild homozygotes (CC) were 1.10 (95% CI 0.44-2.74), 0.95 (95% CI 0.39-2.32) and 0.68 (95% CI 0.28-1.66) in the offspring, fathers and mothers, respectively. The OR between allele (T) versus allele (C) were 1.07 (95% CI 0.72-1.58), 0.98 (95% CI 0.66-1.46) and 0.83 (95% CI 0.56-1.24) in the offspring, fathers and mothers, respectively. T allele could not increase the risk of NSCL/P. For the MTHFR gene C677T variant, transmission disequilibrium test (TDT) analysis yielded no evidence of linkage in the presence of disequilibrium (chi(2) = 1.817, P > 0.05). Results of haplotype-based haplotype relative risk (HHRR) analysis (chi(2) = 1.76, P > 0.05) and family-based association tests (FBAT) (Z = 1.348, P > 0.05) also showed that there was no association between MTHFR C677T variant and the risk of NSCL/P .
No association between genetic polymorphism of MTHFR C677T and NSCLP was observed. Our findings suggest that the MTHFR gene variations C677T do not contribute to the development of NSCLP in Chinese population.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 08/2009; 41(4):432-6.
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ABSTRACT: To study the association of the A2756G polymorphism of the methionine synthase (MS) gene with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Chinese.
Ninety-seven NSCL/P case-parent triads were selected as the case group. One hundred and four healthy subjects and their biological parents were selected as control group. For all subjects the A2756G polymorphism of the MS gene was examined by PCR-RFLP method.
There was no statistical difference in genotype and allele frequencies for MS A2756G variants among family members between case group and control group. The GG genotype was not detected in the offsprings and mothers. The odds ratio and confidence interval of genotype AG in offspring, father and mother were 1.78(0.74-4.34), 0.80(0.36-1.79) and 1.26(0.54-2.93) respectively. The odds ratio and confidence interval of allele G in offspring, father and mother were 1.70(0.78-3.73), 0.88(0.49-1.75), and 1.23(0.59-2.60) respectively. The G allele did not increase the risk of NSCL/P. Transmission disequilibrium test (TDT) analysis yielded no evidence of linkage disequilibrium (chi-square=0.034,P>0.05). The results of haplotype-based haplotype relative risk (HHRR) analysis (chi-square=0.03,P>0.05) and family-based association tests (FBAT) (Z=0.186, P>0.05) failed to show association between the MS A2756G variant and the risk of NSCL/P.
The A2756G polymorphism of the MS gene was not associated with NSCL/P in Chinese in the present study.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 06/2009; 26(3):345-9.
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ABSTRACT: To explore the relationship between genetic polymorphisms of reduced folate carrier (RFC)1 A80G and nonsymdromic cleft lip with or without palate on Chinese population.
There were 97 NSCL/P case-parent triads those were selected as case group. At the same period, 104 healthy subjects were selected together with their biological parents as control group. For all subjects the polymorphisms of RFC1 A80G were examined by PCR-RFLP method.
There was no statistical difference in genotype and gene frequencies for RFC1 A80G variants among family members between case group and control group in offsprings and fathers and mothers (P < 0.05). The odds ratio (OR), confidence interval (CI) and P value of offspring, father and mother genotype (AG) were 0.87 (0.44-1.70), 0.657; 1.09 (0.54-2.21), 0.788; 1.63 (0.79-3.36), 0.152 respectively. The OR, CI and P value of offspring, father and mother allele (GG) were 0.48 (0.19-1.23), 0.094; 0.93 (0.38-2.23), 0.850; 1.30 (0.46-3.67), 0.584 respectively. The OR, CI and P value of offspring, father and mother allele (G) were 1.22 (0.78-1.94), 0.386; 1.02 (0.64-1.61), 0.945; 0.91 (0.58-1.41), 0.660. The G allele could not increase the risk of NSCL/P. But in the transmission disequilibrium test (TDT) analysis, the transmission of the G allele was 40 times, the A allele was 71 times, the A allele was more likely to transmit to the sicken offspring (chi-2 = 8.658, P < 0.05). Results of haplotype-based haplotype relative risk (HHRR) analysis (chi-2 = 10.31, P < 0.05) and family-based association tests (FBAT) ( Z = 2.942, P < 0.05) were showed that there was an association between RFC1 A80G variant and the risk of NSCL/P.
The statistical analysis of nuclear family could evidence of linkage in the presence of disequilibrium, there was an association between RFC1 A80G variant and the risk of NSCL/P, and the A allele could have an association with the dominant high-risk of NSCL/P.
Wei sheng yan jiu = Journal of hygiene research 05/2009; 38(3):276-9.
