The Association of TOX3 Copy Number Variation with Gene Expression and Susceptibility to Nonsyndromic Cleft Lip and/or Palate in a Malay Cohort
https://doi.org/10.21315/aos2025.2002.OA04
- Author:
Noor Areefa Ameera Mohd Ma’amor
1
;
Nurul Syazana Mohamad Shah
1
;
Sarina Sulong
2
;
Nazia Abdul Majid
3
;
Izzeddin Jamil Abualjubain
1
;
Wan Azman Wan Sulaiman
1
Author Information
1. Reconstructive Sciences Unit, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
2. Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
3. Institute of Biological Sciences, Faculty of Sciences, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
- Publication Type:Journal Article
- Keywords:
Cleft lip;
cleft palate;
DNA copy number variations;
gene expression;
TOX3
- From:
Archives of Orofacial Sciences
2025;20(2):151-164
- CountryMalaysia
- Language:English
-
Abstract:
The Association of TOX3 Copy Number Variation with Gene Expression and Susceptibility to Nonsyndromic Cleft Lip and/or Palate in a Malay Cohort:Nonsyndromic cleft lip and/or palate (NSCL/P) is a common congenital malformation with genetic
influences. While Thymocyte selection-associated high mobility group box 3 (TOX3) is involved in
other developmental processes, its role in NSCL/P remained unexplored. This study investigated the
association between TOX3 copy number, expression, and NSCL/P in 64 Malay NSCL/P cases and 64
normal controls. Samples from patients undergoing cleft repair surgery and eligible volunteers for the
control group were quantified via quantitative polymerase chain reactions (qPCR). A higher mean of
TOX3 copy number was found in cases (2.195 ± 0.689) compared to controls (1.962 ± 0.558; p < 0.05).
Similarly, a higher TOX3 expression was observed in cases (0.014 [IQR 0.024]) compared to controls
(0.006 [IQR 0.019]; p < 0.001). Unadjusted analyses showed higher TOX3 copy number (OR = 1.850;
p < 0.05) and its expression associated with NSCL/P. However, these associations were nullified after
adjusting for sex and age (p > 0.05). Instead, male sex emerged as a significant independent predictor for NSCL/P (adjusted OR = 4.03; p < 0.001). Besides, an inverse, weak correlation was observed between TOX3 copy number and expression in NSCL/P patients (ρ = –0.285; p < 0.05) indicating the potential role of epigenetics in this condition. While male sex strongly contributed to the NSCL/P condition, our results suggest that TOX3 is not an independent genetic risk factor for NSCL/P in this population. These results highlight sex as a primary demographic risk factor and underscore the importance of considering demographic context in genetic association studies.
- Full text:2026060917234040921The Association of TOX3.pdf
