Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations.

Autor:	Gowans LJ; Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana Cleft Clinic, Komfo Anokye Teaching Hospital, Kumasi, Ghana Department of Pediatrics, University of Iowa, Iowa City, IA, USA Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA., Adeyemo WL; College of Medicine, University of Lagos, Lagos, Nigeria., Eshete M; Addis Ababa University, Addis Ababa, Ethiopia., Mossey PA; Department of Orthodontics, University of Dundee, Dundee, Scotland., Busch T; Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA., Aregbesola B; Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria., Donkor P; Cleft Clinic, Komfo Anokye Teaching Hospital, Kumasi, Ghana Department of Surgery, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Arthur FK; Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Bello SA; Department of Oral and Maxillofacial Surgery, State House Hospital, Abuja, Nigeria., Martinez A; Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA., Li M; Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA., Augustine-Akpan EA; Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA., Deressa W; Addis Ababa University, Addis Ababa, Ethiopia., Twumasi P; Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Olutayo J; College of Medicine, University of Lagos, Lagos, Nigeria., Deribew M; Addis Ababa University, Addis Ababa, Ethiopia., Agbenorku P; Cleft Clinic, Komfo Anokye Teaching Hospital, Kumasi, Ghana Department of Surgery, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Oti AA; Cleft Clinic, Komfo Anokye Teaching Hospital, Kumasi, Ghana Department of Surgery, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Braimah R; Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria., Plange-Rhule G; Cleft Clinic, Komfo Anokye Teaching Hospital, Kumasi, Ghana., Gesses M; Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia., Obiri-Yeboah S; Cleft Clinic, Komfo Anokye Teaching Hospital, Kumasi, Ghana Department of Surgery, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Oseni GO; Department of Burns and Plastic Surgery, Ladoke Akintola University of Technology Teaching Hospital, Osogbo, Nigeria., Olaitan PB; Department of Burns and Plastic Surgery, Ladoke Akintola University of Technology Teaching Hospital, Osogbo, Nigeria., Abdur-Rahman L; Division of Pediatric Surgery, Department of Surgery, University of Ilorin, Ilorin, Nigeria., Abate F; Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia., Hailu T; Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia., Gravem P; Haukeland University Hospital Bergen, Bergen, Norway., Ogunlewe MO; Department of Burns and Plastic Surgery, Ladoke Akintola University of Technology Teaching Hospital, Osogbo, Nigeria., Buxó CJ; School of Dental Medicine, University of Puerto Rico Medical Science Campus, San Juan, Puerto Rico., Marazita ML; Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA., Adeyemo AA; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Murray JC; Department of Pediatrics, University of Iowa, Iowa City, IA, USA., Butali A; Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA azeez-butali@uiowa.edu.
Jazyk:	angličtina
Zdroj:	Journal of dental research [J Dent Res] 2016 Oct; Vol. 95 (11), pp. 1245-56. Date of Electronic Publication: 2016 Jul 01.
DOI:	10.1177/0022034516657003
Abstrakt:	Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit a multifactorial pattern of inheritance, with genetic and environmental factors both playing crucial roles. Many loci have been implicated in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries, through genome-wide association studies and candidate gene studies. However, few populations of African descent have been studied to date. Here, the authors show evidence of an association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia, and Nigeria). The authors genotyped 48 single-nucleotide polymorphisms that were selected from previous genome-wide association studies and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1,070 unaffected relatives, and 1,078 unrelated controls. The authors also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the case-control analyses of the subpopulations, with West African subpopulations (Ghana and Nigeria) showing a similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, P = 5.10 × 10(-3)), 8q24 (rs987525, P = 1.22 × 10(-3)), and VAX1 (rs7078160, P = 0.04) were nominally associated with NSCL/P, and MSX1 (rs115200552, P = 0.01), TULP4 (rs651333, P = 0.04), CRISPLD2 (rs4783099, P = 0.02), and NOG1 (rs17760296, P = 0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold overtransmission in NSOFC cases through the transmission disequilibrium test and through analyses of the family-based association for disease traits. Through DNA sequencing, the authors also identified 2 novel, rare, potentially pathogenic variants (p.Asn323Asp and p.Lys426IlefsTer6) in ARHGAP29 In conclusion, the authors have shown evidence for the association of many loci with NSCL/P and NSCPO. To the best of this knowledge, this study is the first to demonstrate any of these association signals in any African population. Competing Interests: The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. (© International & American Associations for Dental Research 2016.)
Databáze:	MEDLINE
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