BACKGROUND: The MTHFR rs1801131A>C and rs1801133C>T variants have been analyzed as putative genetic risk factors for oral clefts within various populations worldwide. METHODS: To test the role of these polymorphisms in nonsyndromic cleft lip with or without cleft palate (NSCL/P) in the Brazilian population, we conducted a study combining a Family-Based Association Test (transmission disequilibrium test) and a structured association analysis (case-control study) based on the individual ancestry proportions. The rs1801131 and rs1801133 were initially analyzed in 197 case-parent trios by transmission disequilibrium test, and polymorphisms showing significant association with NSCL/P were subsequently studied in independent sample composed of 318 isolated samples of NSCL/P and 598 healthy controls in a case-control approach. Genomic ancestry was characterized by a set of 40 biallelic short insertion/deletion markers. RESULTS: A strong overtransmission of the T allele of rs1801133 was observed in case-parent trios of NSCL/P (p = 0.002), but no preferential parent-of-origin transmission was detected. No association of rs1801131 polymorphism with NSCL/P was observed. The structured case-control analysis supported that the T allele was significantly more frequent in the NSCL/P group (odds ratio: 1.37; 95% CI: 1.12-1.69; p = 0.002) than in the control group. Both polymorphisms were in linkage disequilibrium (D' = 0.94 and r(2) = 0.79), and haplotype-transmission disequilibrium test for allelic combination of rs1801131 and rs1801133 showed a significant overtransmission of haplotype A-T to the affected NSCL/P offspring (p = 0.001). CONCLUSION: Our findings provide evidences for the involvement of rs1801133 in the development of NSCL/P in the Brazilian population.
BACKGROUND: The MTHFR rs1801131A>C and rs1801133C>T variants have been analyzed as putative genetic risk factors for oral clefts within various populations worldwide. METHODS: To test the role of these polymorphisms in nonsyndromic cleft lip with or without cleft palate (NSCL/P) in the Brazilian population, we conducted a study combining a Family-Based Association Test (transmission disequilibrium test) and a structured association analysis (case-control study) based on the individual ancestry proportions. The rs1801131 and rs1801133 were initially analyzed in 197 case-parent trios by transmission disequilibrium test, and polymorphisms showing significant association with NSCL/P were subsequently studied in independent sample composed of 318 isolated samples of NSCL/P and 598 healthy controls in a case-control approach. Genomic ancestry was characterized by a set of 40 biallelic short insertion/deletion markers. RESULTS: A strong overtransmission of the T allele of rs1801133 was observed in case-parent trios of NSCL/P (p = 0.002), but no preferential parent-of-origin transmission was detected. No association of rs1801131 polymorphism with NSCL/P was observed. The structured case-control analysis supported that the T allele was significantly more frequent in the NSCL/P group (odds ratio: 1.37; 95% CI: 1.12-1.69; p = 0.002) than in the control group. Both polymorphisms were in linkage disequilibrium (D' = 0.94 and r(2) = 0.79), and haplotype-transmission disequilibrium test for allelic combination of rs1801131 and rs1801133 showed a significant overtransmission of haplotype A-T to the affected NSCL/P offspring (p = 0.001). CONCLUSION: Our findings provide evidences for the involvement of rs1801133 in the development of NSCL/P in the Brazilian population.
Keywords:
MTHFR polymorphism; case-control study; nonsyndromic cleft lip with or without cleft palate; rs1801131; rs1801133; transmission disequilibrium test
Authors: L J J Gowans; W L Adeyemo; M Eshete; P A Mossey; T Busch; B Aregbesola; P Donkor; F K N Arthur; S A Bello; A Martinez; M Li; E A Augustine-Akpan; W Deressa; P Twumasi; J Olutayo; M Deribew; P Agbenorku; A A Oti; R Braimah; G Plange-Rhule; M Gesses; S Obiri-Yeboah; G O Oseni; P B Olaitan; L Abdur-Rahman; F Abate; T Hailu; P Gravem; M O Ogunlewe; C J Buxó; M L Marazita; A A Adeyemo; J C Murray; A Butali Journal: J Dent Res Date: 2016-07-01 Impact factor: 8.924