title: Association of BMP4 polymorphisms with non-syndromic cleft lip with or without cleft palate and isolated cleft palate in Latvian and Lithuanian populations.
abstract: Cleft lip with or without cleft palate (CLP and CL, respectively) and isolated cleft palate (CP) represent one of the most common human birth defects, with a prevalence of approximately 1 in 300-2500 depending on the population. Formation of non-syndromic CL/CLP and CP arises from the interaction of environmental and genetic factors. The objective of this study was to investigate the association between the BMP4 gene (encoding bone morphogenetic protein 4) and non-syndromic CL/CLP and CP in order to clarify the role of this gene in the aetiology of the malformation in Latvian and Lithuanian populations. We genotyped three markers of the BMP4 gene (rs17563, rs2071047 and rs1957860) in order to perform single marker and haplotype association analyses for Latvian and Lithuanian non-syndromic CL/CLP and CP patients and controls. Transmission disequilibrium test was also conducted for Latvian and Lithuanian proband-parent trios. The case-control analysis revealed that SNP rs2071047 allele A was associated with a decreased risk of CL/CLP in the Latvian population, which was confirmed by the haplotype analysis. A modest association was detected between SNP rs1957860 and CP in the Lithuanian population, where allele C was associated with a decreased risk of this cleft phenotype, corroborating haplotype analysis data. Our findings support a role of the BMP4 gene in the aetiology of non-syndromic CL/CLP and CP in the studied populations.
authors.affiliation: Scientific Laboratory of Molecular Genetics, Rīga Stradiņš University, Dzirciema street 16, LV-1007, Riga, Latvia. inga.kempa@rsu.lv.
authors.forename: Inga
authors.initials: I
authors.lastname: Kempa
authors.forename: Laima
authors.initials: L
authors.lastname: Ambrozaitytė
authors.forename: Janis
authors.initials: J
authors.lastname: Stavusis
authors.forename: Ilze
authors.initials: I
authors.lastname: Akota
authors.forename: Biruta
authors.initials: B
authors.lastname: Barkane
authors.forename: Astrida
authors.initials: A
authors.lastname: Krumina
authors.forename: Aušra
authors.initials: A
authors.lastname: Matulevičienė
authors.forename: Algirdas
authors.initials: A
authors.lastname: Utkus
authors.forename: Vaidutis
authors.initials: V
authors.lastname: Kučinskas
authors.forename: Baiba
authors.initials: B
authors.lastname: Lace
mesh_terms: D000225:Adenine; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D016022:Case-Control Studies; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D003596:Cytosine; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006147:Guanine; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D007844:Latvia; D015810:Linkage Disequilibrium / Q000235:genetics; D008097:Lithuania; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013941:Thymine
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D005819:Genetic Markers; D006147:Guanine; D003596:Cytosine; D000225:Adenine; D013941:Thymine