Environmental and genetic factors in etiology of orofacial clefts in Argentina

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Family-based association study of the MTHFR polymorphism C677T in patients with nonsyndromic cleft lip and palate from central Europe.

Item does not contain fulltextOBJECTIVE: The 677C-->T allele in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been implicated in the etiology of nonsyndromic cleft lip and palate (CL/P). This study involved a family-based association study of the MTHFR polymorphism. PATIENTS/PARTICIPANTS: We examined 181 patients with CL/P of central European descent and their parents for this variant. RESULTS: The transmission disequilibrium test (TDT) did not confirm an association between the MTHFR 677C-->T polymorphism and nonsyndromic CL/P as previously suggested (p = .36). When comparing the offspring of mothers with periconceptional use of folate to those without, no statistically significant differences were found (p = .708). CONCLUSION: Our data suggest that the MTHFR 677C-->T polymorphism does not make a major contribution to the occurrence of CL/P among central Europeans

Genetic studies in the nigerian population implicate an MSX1 mutation in complex oral facial clefting disorders

BACKGROUND: Orofacial clefts are the most common malformations of the head and neck with a World-wide prevalence of 1/700 births. They are commonly divided into CL(P) and CP based on anatomical, genetic and embryological findings. A Nigerian craniofacial anomalies study “NigeriaCRAN” was set up in 2006 to investigate the role of gene-environment interaction in the etiology of orofacial clefts in Nigeria. SUBJECTS AND METHODS: DNA isolated from saliva from the Nigerian probands was used for genotype association studies and direct sequencing on the cleft candidate genes: MSX1, IRF6, FOXE1, FGFR1, FGFR2, BMP4, MAFB, ABCA4, PAX7 and VAX1, and the chromosome 8q region. RESULTS: A missense mutation A34G in MSX1 was observed in nine cases and four hap map controls. No other apparent etiologic variations were identified. A deviation from HWE was observed in the cases (p= 0.00002). There was a significant difference between the affected side for unilateral CL (p=0.03) and, between bilateral clefts and clefts on either side (p=0.02). A significant gender difference was also observed for CP (p=0.008). CONCLUSIONS: The replication of a mutation previously implicated in other populations suggests a role for the MSX1 A34G variant in the etiology of CL(P)

Environmental Risk Factors in the Etiology of Nonsyndromic Orofacial Clefts in the Western Region of Saudi Arabia

Objectives Nonsyndromic orofacial cleft (NSOFC) etiology is multifactorial and heterogeneous. This study aimed to identify environmental risk factors related to NSOFC in the Western Region of Saudi Arabia. Methods A case-control study carried out in seven hospitals in two main cities (Jeddah and Maddina) over 2 years on parents of 112 infants with NSOFC (infants were also examined) and 138 infant controls, matched for age (≤18 months), gender, and location, completed a questionnaire on 3-month pregestation and first trimester events. Results There was significantly increased NSOFC risk with twin pregnancies (P = .01, odds ratio [OR] = 9.5, 95% confidence interval [CI]: 1.15 to 78.4), maternal antibiotic use (P = .021, OR = 2.71, 95% CI: 1.11 to 6.62), antiemetic medication (P = .005, OR = 2.85, 95% CI: 1.3 to 6), severe morning sickness (P = .006, OR = 3.6, 95% CI: 1.34 to 9.65), illness (P = .009, OR = 2.19, 95% CI: 1.17 to 4.08), common cold/flu (P = .003, OR = 3.32, 95% CI: 1.48 to 7.58), Jorak smoking (P = .004, OR = 14.07, 95% CI: 1.55 to 128.1), and passive smoking (P = .05, OR = 2.05, 95% CI: 1.05 to 4.01). Reduced NSOFC risk was found with calcium supplementation (P = .02, OR = 0.32, 95% CI: 0.11 to 0.88), incense use (P = .03, OR = 0.58, 95% CI: 0.34 to 0.98), and maternal drinking water, with Zamzam water (which contains a high concentration of minerals) showing a significant protective effect compared with tap water (P = .01, 95% CI: 0.06 to 0.6) and bottled water (P = .02, 95% CI: 0.03 to 0.57). Conclusion Twin births, maternal antibiotic use, antiemetic medication, severe morning sickness, common cold/flu, Jorak smoking, and passive smoking were associated with infants born with NSOFC. Calcium supplementation, incense use, and Zamzam water reduced the risk of NSOFC, raising the possibility of community preventive programs