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Stomatologija 2014; 16 (3): 94-101 390 KB

Association of BMP4 polymorphisms with non-syndromic cleft lip with or without cleft palate and isolated cleft palate in Latvian and Lithuanian populations

Inga Kempa, Laima Ambrozaitytė, Janis Stavusis, Ilze Akota, Biruta Barkane, Astrida Krumina, Aušra Matulevičienė, Algirdas Utkus, Vaidutis Kučinskas, Baiba Lace

Summary

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.

This work was supported by Latvian Science Council grant No. 09.1115 and European Social Fund project No. 2009/0147/1DP/1.1.2.1.2/09/ IPIA/VIAA/009.

Key words: BMP4 gene, non-syndromic clefts, case-control analysis, haplotype analysis, TDT analysis.

Received: 06 11 2013

Accepted for publishing: 26 09 2014

¹Scientific Laboratory of Molecular Genetics, Rīga Stradiņš University, Riga, Latvia

²Latvian Biomedical Research and Study Centre, Riga, Latvia

³Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, Vilnius, Lithuania

⁴Centre for Medical Genetics at Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania

⁵Institute of Stomatology, Rīga Stradiņš University, Riga, Latvia

Inga Kempa^{1. 2} – PhD

Laima Ambrozaitytė^{3. 4} – PhD

Janis Stavusis² – scientific assist.

Ilze Akota⁵ – PhD, M.D.

Biruta Barkane⁵ – PhD, M.D.

Astrida Krumina² – Dr. habil., PhD, M.D.

Aušra Matulevičienė^{3. 4} – PhD, M.D.

Algirdas Utkus^{3. 4} – PhD, M.D.

Vaidutis Kučinskas^{3. 4} – Dr. habil., PhD

Baiba Lace² – PhD, M.D.

Address correspondence to Dr. Inga Kempa, Scientific Laboratory of Molecular Genetics, Rīga Stradiņš University, Dzirciema street 16, LV-1007, Riga, Latvia.

E-mail address: inga.kempa@rsu.lv



	Baltic Dental and Maxillofacial Journal

September, 2014, Vol. 16, No. 3 CONTENTS SCIENTIFIC ARTICLES Validation of a Latvian and a Russian version of the Oral Health Impact Profile for use among adults Jolanta Pugaca, Ilga Urtane, Pertti Pirttiniemi, Irena Rogovska 83-86 The relationship between unilateral mandibular angle fracture and temporomandibular joint function Ausra Baltrusaityte, Algimantas Surna, Gaivile Pileicikiene, Ricardas Kubilius, Alvydas Gleiznys, Juozas Zilinskas 87-93 Association of BMP4 polymorphisms with non-syndromic cleft lip with or without cleft palate and isolated cleft palate in Latvian and Lithuanian populations Inga Kempa, Laima Ambrozaitytė, Janis Stavusis, Ilze Akota, Biruta Barkane, Astrida Krumina, Aušra Matulevičienė, Algirdas Utkus, Vaidutis Kučinskas, Baiba Lace 94-101 Symmetry of external auditive meatus. A pilot study on human skulls Simona Mizgiryte, Julius Vaitelis, Arunas Barkus, Linas Zaleckas, Rolandas Pletkus, Adomas Auskalnis 102-108 REVIEWS The upper airway dimensions in different sagittal craniofacial patterns: a systematic review Iveta Indriksone, Gundega Jakobsone 109-117 The complication of oral piercing and the role of dentist in their prevention: a literature review Cinzia Maspero, Giampietro Farronato, Lucia Giannini, Laima Kairyte, L. Pisani, Guido Galbiati 118-124 © 2014 Stomatologija		Stomatologija 2014; 16 (3): 94-101 390 KB Association of BMP4 polymorphisms with non-syndromic cleft lip with or without cleft palate and isolated cleft palate in Latvian and Lithuanian populations Inga Kempa, Laima Ambrozaitytė, Janis Stavusis, Ilze Akota, Biruta Barkane, Astrida Krumina, Aušra Matulevičienė, Algirdas Utkus, Vaidutis Kučinskas, Baiba Lace Summary 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. This work was supported by Latvian Science Council grant No. 09.1115 and European Social Fund project No. 2009/0147/1DP/1.1.2.1.2/09/ IPIA/VIAA/009. Key words: BMP4 gene, non-syndromic clefts, case-control analysis, haplotype analysis, TDT analysis. Received: 06 11 2013 Accepted for publishing: 26 09 2014 ¹Scientific Laboratory of Molecular Genetics, Rīga Stradiņš University, Riga, Latvia ²Latvian Biomedical Research and Study Centre, Riga, Latvia ³Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, Vilnius, Lithuania ⁴Centre for Medical Genetics at Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania ⁵Institute of Stomatology, Rīga Stradiņš University, Riga, Latvia Inga Kempa^{1. 2} – PhD Laima Ambrozaitytė^{3. 4} – PhD Janis Stavusis² – scientific assist. Ilze Akota⁵ – PhD, M.D. Biruta Barkane⁵ – PhD, M.D. Astrida Krumina² – Dr. habil., PhD, M.D. Aušra Matulevičienė^{3. 4} – PhD, M.D. Algirdas Utkus^{3. 4} – PhD, M.D. Vaidutis Kučinskas^{3. 4} – Dr. habil., PhD Baiba Lace² – PhD, M.D. Address correspondence to Dr. Inga Kempa, Scientific Laboratory of Molecular Genetics, Rīga Stradiņš University, Dzirciema street 16, LV-1007, Riga, Latvia. E-mail address: inga.kempa@rsu.lv