PT  - JOURNAL ARTICLE
AU  - Goffinet, Laetitia
AU  - Oussalah, Abderrahim
AU  - Guéant-Rodriguez, Rosa-Maria
AU  - Chery, Céline
AU  - Basha, Mirta
AU  - Avogbe, Patrice Hodonou
AU  - Josse, Thomas
AU  - Jeannesson, Elise
AU  - Rouyer, Pierre
AU  - Flayac, Justine
AU  - Gerard, Philippe
AU  - Le Touze, Anne
AU  - Bonin-Goga, Béatrice
AU  - Goga, Dominique
AU  - Simon, Etienne
AU  - Feillet, François
AU  - Vikkula, Miikka
AU  - Guéant, Jean-Louis
TI  - Cystathionine β-synthase genetic variant rs2124459 is associated with a reduced risk of cleft palate in French and Belgian populations
AID  - 10.1136/jmedgenet-2016-104111
DP  - 2016 Dec 01
TA  - Journal of Medical Genetics
PG  - 828--834
VI  - 53
IP  - 12
4099  - http://jmg.bmj.com/content/53/12/828.short
4100  - http://jmg.bmj.com/content/53/12/828.full
SO  - J Med Genet2016 Dec 01; 53
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.