rs1801133C>T polymorphism in MTHFR is a risk factor for nonsyndromic cleft lip with or without cleft palate in the Brazilian population.

Autor: de Aguiar PK; Graduate Program in Molecular and Celular Biology - Federal University of Paraíba, João Pessoa, Paraíba, Brazil., Coletta RD, de Oliveira AM, Machado RA, Furtado PG, de Oliveira LA, de Aquino SN, Martelli-Junior H, de Almeida Reis SR, Moreira HS, Persuhn DC
Jazyk: angličtina
Zdroj: Birth defects research. Part A, Clinical and molecular teratology [Birth Defects Res A Clin Mol Teratol] 2015 Apr; Vol. 103 (4), pp. 292-8. Date of Electronic Publication: 2015 Mar 24.
DOI: 10.1002/bdra.23365
Abstrakt: 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.
(© 2015 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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