Molecular Screening of VAX1 Gene Polymorphisms Uncovered the Genetic Heterogeneity of Nonsyndromic Orofacial Cleft Among Saudi Arabian Patients

Heba Jafar Sabbagh; Nicola P.T Innes; Sherif Edris Ahmed; Azeez Butali; Eman Abdulbaset Alnamnakani; Sari M Rabah; Mustafa A Hamdan; Nasir H Alhamlan; Fatma Dawood Abdulhameed; Mona Hassan Ahmed Hassan; Hadiah Bassam Al Mahdi; Najlaa M Alamoudi; Jumana Y Al-Aama; Sumer M Alaki; Peter A Mossey

doi:10.1089/gtmb.2018.0207

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Molecular Screening of VAX1 Gene Polymorphisms Uncovered the Genetic Heterogeneity of Nonsyndromic Orofacial Cleft Among Saudi Arabian Patients

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Molecular Screening of VAX1 Gene Polymorphisms Uncovered the Genetic Heterogeneity of Nonsyndromic Orofacial Cleft Among Saudi Arabian Patients

Heba Jafar Sabbagh, Nicola P.T Innes, Sherif Edris Ahmed, Azeez Butali, Eman Abdulbaset Alnamnakani, Sari M Rabah, Mustafa A Hamdan, Nasir H Alhamlan, Fatma Dawood Abdulhameed, Mona Hassan Ahmed Hassan, …

Genetic testing and molecular biomarkers, Vol.23(1), pp.45-50

01/01/2019

DOI: 10.1089/gtmb.2018.0207

PMID: 30633559

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Abstract

Objective: Nonsyndromic orofacial cleft (NSOFC) including cleft lip with or without cleft palate (CL±P) and cleft palate (CP) are multifactorial developmental disorders with both genetic and environmental etiological factors. In this study we investigated the association between CL±P and CP, and two polymorphisms previously determined using genome-wide association studies, as well as the association between consanguinity and CL±P and CP. Methods: DNA was extracted from saliva specimens from 171 triads consisting of affected individuals and their parents, as well as 189 control triads (matched for age, gender, and location) that were recruited from 11 referral hospitals in Saudi Arabia. Two polymorphisms, rs4752028 and rs7078160, located in the VAX1 gene were genotyped using real-time polymerase chain reaction. A transmission disequilibrium test was carried out using the Family-Based Association Test and PLINK (genetic tool-set) to measure the parent-of-origin effect. Results: Significant differences were found between affected individuals and the control group. In the case of the rs4752028 risk allele in cleft, the phenotypes were: CL±P (fathers: odds ratio [OR] 2.16 [95% CI 1.38–3.4]; mothers: OR 2.39 [95% CI 1.53–3.71]; and infants: OR 2.77 [95% CI 1.77–4.34]) and CP (fathers: OR 2.24 [95% CI 1.15–4.36] and infants: OR 2.43 [95% CI 1.25–4.7]). For CL±P and the rs7078160 risk allele, the phenotypes were: (fathers: OR 1.7 [95% CI 1.05–2.86]; mothers: OR 2.43 [95% CI 1.49–3.97]; and infants: OR 2.34 [95% CI 1.44–3.81]). In terms of consanguinity, we found significant association between consanguinity and the rs4752028 polymorphism minor allele among CL±P compared with controls ( p = 0.001). Conclusion: This is the first study to find a relationship between these two loci on 10q25 (rs4752028 and rs7078160) and NSOFC in a population with high levels of consanguinity.

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Title: Subtitle: Molecular Screening of VAX1 Gene Polymorphisms Uncovered the Genetic Heterogeneity of Nonsyndromic Orofacial Cleft Among Saudi Arabian Patients
Creators: Heba Jafar Sabbagh - 1Department of Pediatric Dentistry, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia
Nicola P.T Innes - 2School of Dentistry, University of Dundee Dental School, Dundee, Scotland, United Kingdom
Sherif Edris Ahmed - 4Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
Azeez Butali - 5Department of Oral Pathology, Radiology and Medicine, Dows Institute for Dental Research, College of Dentistry, University of Iowa, Iowa City, Iowa
Eman Abdulbaset Alnamnakani - 6Prince Sultan Military Medical City, Head of Cleft Lip and Palate Unit, Riyadh Military Hospital, Riyadh, Saudi Arabia
Sari M Rabah - 8Faculty of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
Mustafa A Hamdan - 9Department of Plastic Surgery, King Saud Medical City, Ministry of Health, Riyadh, Saudi Arabia
Nasir H Alhamlan - 10Pediatric Dentistry and Orthodontic Residency Program, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
Fatma Dawood Abdulhameed - 11Department of Pediatric Surgery, Madina Maternity and Children's Hospital, Madina, Saudi Arabia
Mona Hassan Ahmed Hassan - 13Department of Biostatistics, High Institute of Public Health, Alexandria University, Alexandria, Egypt
Hadiah Bassam Al Mahdi - 14Princess Al-Jawhara Albarhim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia
Najlaa M Alamoudi - 1Department of Pediatric Dentistry, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia
Jumana Y Al-Aama - 15Department of Genetic Medicine, Faculty of Medicine and Princess Al Jawhara Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia
Sumer M Alaki - 1Department of Pediatric Dentistry, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia
Peter A Mossey - 16WHO Collaborating Centre, University of Dundee Dental School, Dundee, Scotland
Resource Type: Journal article
Publication Details: Genetic testing and molecular biomarkers, Vol.23(1), pp.45-50
DOI: 10.1089/gtmb.2018.0207
PMID: 30633559
NLM abbreviation: Genet Test Mol Biomarkers
ISSN: 1945-0265
eISSN: 1945-0257
Publisher: Mary Ann Liebert, Inc., publishers
Language: English
Date published: 01/01/2019
Academic Unit: Oral Pathology, Radiology and Medicine; Stead Family Department of Pediatrics; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9984065722602771

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