Association studies of candidate genes and cleft lip and palate taking into consideration geographical origin

• Published in: European journal of oral sciences Vol. 119; no. 6; pp. 413 - 417
• Main Authors: Lace, Baiba, Kempa, Inga, Piekuse, Linda, Grinfelde, Ieva, Klovins, Janis, Pliss, Liana, Krumina, Astrida, Vieira, Alexandre R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2011
• Subjects: alpha 2; Case-Control Studies; Cleft Lip - ethnology; Cleft Lip - genetics; Cleft Palate - ethnology; Cleft Palate - genetics; collagen; Collagen Type XI - genetics; collagen, type XI, alpha 2; Databases, Genetic; DNA, Mitochondrial - genetics; Ethnic Groups - genetics; Female; fibroblast growth factor receptor 1; Genetic Association Studies; Haplotypes - genetics; Humans; Latvia - ethnology; Latvian population; Male; Reference Values; type XI; WNT3; Wnt3 Protein - genetics; Latvia
• ISSN: 0909-8836; 1600-0722; 1600-0722
• DOI: 10.1111/j.1600-0722.2011.00877.x

Lace B, Kempa I, Piekuse L, Grinfelde I, Klovins J, Pliss L, Krumina A, Vieira AR. Association studies of candidate genes and cleft lip and palate taking into consideration geographical origin. 
 Eur J Oral Sci 2011; 119: 413–417. © 2011 Eur J Oral Sci 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.