[Association between platelet-derived growth factor-C single nucleotide polymorphisms and nonsyndromic cleft lip with or without cleft palate in Western Chinese population].

OBJECTIVE: To explore the association between two single nucleotide polymorphisms (SNPs), namely, rs4691383 and rs7667857, in the platelet-derived growth factor-C (PDGF-C) gene, the genotypes, environmental exposure factors, and nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Western Chinese population. METHODS: A total of 268 case-parent trios were selected, and two SNPs (rs4691383 andrs7667857) were genotyped by using polymerase chain reaction and restriction enzyme fragment length polymorphic method and direct sequencing method. Hardy-Weinberg equilibrium, linkage disequilibrium test, transmission disequilibrium test, and haplotype analysis were conducted to analyze the data. Meanwhile, the questionnaires on the epidemiology of cleft lip and palate filled by the included samples were collected, and the interaction between the genotypes of the two SNPs and environmental exposure factors was assessed by conditional logistic regression. RESULTS: The A allele at rs4691383 and the G allele at rs7667857 of PDGF-C gene were over-transmitted for NSCL/P (P<0.05). No interaction effect was observed between the three environmental exposure factors (history of smoking/passive smoking, folic acid supplementation, and long-term inhalation of harmful environmental gases) and the PDGF-C genotypes among NSCL/P (P>0.05). CONCLUSIONS: The rs4691383 and rs7667857 at PDGF-C gene are closely related to the occurrence of NSCL/P in Western Chinese population. However, the interaction between environmental exposure factors and PDGF-C genotypes is not obvious in the occurrence of NSCL/P.

Evaluation of the association of polymorphisms in EYA1, environmental factors, and non-syndromic orofacial clefts in Western Han Chinese.

BACKGROUND: Non-syndromic orofacial clefts (NSOCs) are complex disease involving genetic triggers, environmental factors, and their interplay. Recent studies demonstrated that EYA1, a member of eye absent gene family, might contribute to NSOCs. METHODS: We investigated three single nucleotide polymorphisms (SNPs) and eight environmental factors (multivitamin, folic acid and calcium supplementation history, maternal alcohol consumption, common cold history, maternal smoking and environmental tobacco smoke in the first trimester, and paternal smoking in the 3 months before pregnancy) among 294 case-parent trios and 183 individual controls in western Han Chinese to evaluate the relationship between EYA1, environmental factors, and NSOCs. To be better known the gene's role in the etiology of NSOCs, we performed statistical analysis in different aspects including the linkage disequilibrium test, transmission disequilibrium test, haplotype analysis, multiple logistic regression analysis, and conditional logistic regression analysis. RESULTS: Allele C at rs3779748 showed an over-transmission in NSCL/P trios (P = 0.03), and genotype A/A at rs10094908 was under-transmitted among NSCL/P trios (P = 0.03), whereas over-transmitted among NSCPO trios (P = 0.02). The haplotype GC of rs10094908-rs3779748 was over-transmitted among NSCL/P trios (P = 0.05) and NSCPO trios (P = 0.05), respectively. Maternal common cold history, environmental tobacco smoke, and maternal alcohol consumption during the first trimester of pregnancy were risk factors for NSOCs, while calcium supplementation during the first trimester showed a protective effect. No evidence of interactions between EYA1 and environmental factors was found. CONCLUSIONS: These results revealed an association between EYA1, some environmental factors, and NSOCs in western Han Chinese.

Association among polymorphisms at MYH9, environmental factors, and nonsyndromic orofacial clefts in western China.

Myosin heavy chain 9, nonmuscle (MYH9) and environmental factors have been shown to be associated with nonsyndromic cleft lip with or without cleft palate in several populations. Our study aimed to confirm the contribution of MYH9 and environmental factors to nonsyndromic orofacial cleft risk in western Han Chinese. Four single-nucleotide polymorphisms were investigated in 180 case trios and 224 normal peers in western China using transmission disequilibrium test, family-based association test analysis, and logistic regression models. Strong evidence of linkage disequilibrium was found between these markers and the disease by both single-nucleotide polymorphism analysis (G allele at rs2269529 and T allele at rs16996652) and haplotype analysis (G-T [for rs2269529 and rs16996652] and G-A-T [for rs2269529, rs3752462, and rs16996652] among others). Mothers' illness, medication, and passive smoking during the first trimester may increase the risk of nonsyndromic orofacial clefts, but mothers' vitamin (including folic acid) supplementation during the first trimester is a protective factor. Interactions between mothers' passive smoking during the first trimester and T/T genotype of rs16996652 had statistical significance. Risk factors identified in our study may provide a better understanding of the etiological role of MYH9 and influence of environmental factors in nonsyndromic orofacial cleft incidence.

Association among IRF6 polymorphism, environmental factors, and nonsyndromic orofacial clefts in western china.

The interferon regulatory factor 6 (IRF6) gene and environmental factors have been shown to be associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in several populations. This study aimed to confirm the contribution of IRF6 and environmental factors to NSCL/P risk in western Han Chinese. Five single nucleotide polymorphisms (SNPs) were investigated in 107 case trios (child and parents) and 100 normal peers in western China using transmission disequilibrium test, case-control analysis, and logistic regression models. Strong evidence of linkage disequilibrium was found between these markers and the disease in both SNP analysis (A allele at rs4844880, G allele at rs2073485, and C allele at rs599021) and haplotype analysis (A-A for rs861019 and rs4844880, A-C for rs4844880 and rs599021, among others). Both mothers' medication and passive smoking during the first trimester of pregnancy may increase the risk of NSCL/P, but mothers' vitamins (including folic acid) supplementation during the first trimester was a protective factor. Interactions between mothers' abortion history and TT genotype of rs2235373 were statistically significant (odds ratio = 6.70, 95% confidence interval =1.69-26.52). Risk factors identified in this study may provide a better understanding of the etiological role IRF6 and environmental factors play in NSCL/P incidence.