title: Association studies of candidate genes and cleft lip and palate taking into consideration geographical origin.
abstract: Isolated cleft lip and/or palate (CL/CLP) is a complex congenital anomaly with many contributing factors. There are several genes involved in the aetiology of CL/CLP, they are different in selected populations. In a previous study, the mitochondrial haplotypes of Latvian subjects with CL/CLP were characterized. Latvian subjects with CL/CLP have mostly mitochondrial haplogroups U4/U5 compared with the ethnic population of Latvia. The aim of this study was to stratify the results of genotyping based on European mitochondrial DNA (mtDNA) haplotypes. DNA samples from 108 patients with CL/CLP and from 182 unrelated and unaffected individuals selected randomly in Latvia (used as controls) were obtained for investigation. In this study, we analysed the data taking into consideration mitochondrial haplogroups and found that gene associations depended on the genetic origin of the population. The phenotype of patients with non-U haplotypes was associated with markers in wingless-type MMTV integration site family, member 3 (WNT3), collagen, type XI, alpha 2 (COL11A2), and fibroblast growth factor receptor 1 (FGFR1), whereas patients with U4 and U5 haplotypes showed significant association with WNT3 and COL11A2. It is unlikely that mtDNA variants play a direct role in the development of CL/CLP; rather, they may be a surrogate for population substructure and provide a tool to increase homogeneity and statistical power.
authors: Latvian Biomedical Study and Research Centre, Riga, Latvia. baiba.lace@gmail.com
authors: Baiba
authors: B
authors: Lace
authors: Inga
authors: I
authors: Kempa
authors: Linda
authors: L
authors: Piekuse
authors: Ieva
authors: I
authors: Grinfelde
authors: Janis
authors: J
authors: Klovins
authors: Liana
authors: L
authors: Pliss
authors: Astrida
authors: A
authors: Krumina
authors: Alexandre R
authors: AR
authors: Vieira
mesh_terms: D016022:Case-Control Studies; D002971:Cleft Lip / Q000208:ethnology / Q000235:genetics*; D002972:Cleft Palate / Q000208:ethnology / Q000235:genetics*; D024161:Collagen Type XI / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D030541:Databases, Genetic; D005006:Ethnicity / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007844:Latvia / Q000208:ethnology; D008297:Male; D012016:Reference Values; D060508:Wnt3 Protein / Q000235:genetics*
chemical_list: C499319:COL11A2 protein, human; D024161:Collagen Type XI; D004272:DNA, Mitochondrial; C555507:WNT3 protein, human; D060508:Wnt3 Protein