RT Journal Article
SR Electronic
T1 Cystathionine β-synthase genetic variant rs2124459 is associated with a reduced risk of cleft palate in French and Belgian populations
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 828
OP 834
DO 10.1136/jmedgenet-2016-104111
VO 53
IS 12
A1 Laetitia Goffinet
A1 Abderrahim Oussalah
A1 Rosa-Maria Guéant-Rodriguez
A1 Céline Chery
A1 Mirta Basha
A1 Patrice Hodonou Avogbe
A1 Thomas Josse
A1 Elise Jeannesson
A1 Pierre Rouyer
A1 Justine Flayac
A1 Philippe Gerard
A1 Anne Le Touze
A1 Béatrice Bonin-Goga
A1 Dominique Goga
A1 Etienne Simon
A1 François Feillet
A1 Miikka Vikkula
A1 Jean-Louis Guéant
YR 2016
UL http://jmg.bmj.com/content/53/12/828.abstract
AB Background Orofacial cleft (OFC) is the most prevalent craniofacial birth defect. Genes involved in one-carbon, folate and vitamin B12 metabolisms have been associated with OFC but no study performed a concomitant assessment on genes involved in these three pathways.Objective We looked for potential genetic variants associated with OFC using an exhaustive gene panel of one-carbon metabolism.Methods We performed a case–control discovery study on children with OFC (236 cases, 145 controls) and their related mothers (186 cases, 127 controls). We performed a replication study on the top significant genetic variant in an independent group from Belgium (248 cases, 225 controls).Results In the discovery study on ‘mothers’, the CBS locus reached array-wide significance (p=9.13×10−6; Bonferroni p=4.77×10−3; OR 0.47 (0.33 to 0.66)) among the 519 haplotypes tested for their association with OFC risk. Within the CBS haplotype block (rs2124459, rs6586282, rs4920037, rs234705, rs234709), the rs2124459 was the most significantly associated with a reduced risk of OFC (p=1.77×10−4; Bonferroni p=2.00×10−2; OR 0.53 (0.38 to 0.74), minor allele). The rs2124459 was associated with a reduced risk of cleft palate (CP) (p=6.78×10−5; Bonferroni p=7.80×10−3; OR 0.40 (0.25 to 0.63)). In the ‘children’ group, the rs2124459 was associated with a reduced risk of CP (p=0.02; OR 0.61 (0.40 to 0.93), minor allele). The association between rs2124459 and reduced risk of CP was replicated in an independent children population from Belgium (p=0.02; OR 0.64 (0.44 to 0.93), minor allele).Conclusions The CBS rs2124459 was associated with a reduced risk of CP in both French and Belgian populations. These results highlight the prominent involvement of the vitamin B6-dependent transsulfuration pathway of homocysteine in OFC risk and the interest for evaluating vitamin B6 status in further population studies.