Zhong-Lin Jia1, Sha He2, Shu-Yuan Jiang3, Bi-He Zhang3, Shi-Jun Duan3, Jia-Yu Shi4, Ning Huang3, Wen-Chao Zhu3, Bing Shi5. 1. State Key Laboratory of Oral Disease, West China hospital of Stomatology, Sichuan University, Chengdu, PR China. 2. State Key Laboratory of Oral Disease, West China hospital of Stomatology, Sichuan University, Chengdu, PR China; Department of Cleft Lip and Palate Surgery, West China College of Stomatology, Sichuan University, Chengdu, PR China; Department of Stomatology, The third People's hospital of Chengdu, Chengdu, PR China. 3. State Key Laboratory of Oral Disease, West China hospital of Stomatology, Sichuan University, Chengdu, PR China; Department of Cleft Lip and Palate Surgery, West China College of Stomatology, Sichuan University, Chengdu, PR China. 4. Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, CA 90095, United States. 5. State Key Laboratory of Oral Disease, West China hospital of Stomatology, Sichuan University, Chengdu, PR China; Department of Cleft Lip and Palate Surgery, West China College of Stomatology, Sichuan University, Chengdu, PR China. Electronic address: zhonglinjia@sina.com.
Abstract
OBJECTIVE: Non-syndromic orofacial cleftings (NSOCs) are considered as complex trait, which results from genetic and/or environmental modifiers. Current findings could only explain small portion of the NSOCs. SOX9 gene plays an important role during craniofacial development in animal models and the Pierre Robin sequence (PRS). However, its role in non-syndromic clefts remains unknown. DESIGN: In this study, we selected eight SNPs in and around SOX9 gene to make maximum coverage, and genotyped them by using RFLP-PCR and ligase detection reaction (LDR) methods to test its associations among 151 NSOCs (53 NSCLP, 52 NSCLO and 46 NSCPO) from Western Han Chinese population. RESULTS: Allelic TDT results showed that G allele at rs12941170 of SOX9 was under-transmitted among NSOCs (p=0.00014, OR=0.55 and 95%CI: 0.40-0.75), which could indicate that the G allele is protective against NSOCs; parent-of-origin effect analysis showed that G allele at rs12941170 was maternally under-transmitted (p=0.002), while there was no statistically difference between the maternal and paternal transmission of it. To test if the adjacent SNPs travel together from parents to the affected individual, we carried out the sliding window haplotype analysis, it is interesting to find that the haplotypes carrying the G allele at rs12941170 also was under-transmitted for NSOCs, NSCL/P, NSCLP and NSCPO (lowest p=0.00033). CONCLUSIONS: This study suggested that G allele at rs12941170 was protective, which could decrease the risk for NSOCs from Western Han Chinese population, and it will provide new reference for future research and genetic counseling in NSOCs.
OBJECTIVE:Non-syndromic orofacial cleftings (NSOCs) are considered as complex trait, which results from genetic and/or environmental modifiers. Current findings could only explain small portion of the NSOCs. SOX9 gene plays an important role during craniofacial development in animal models and the Pierre Robin sequence (PRS). However, its role in non-syndromic clefts remains unknown. DESIGN: In this study, we selected eight SNPs in and around SOX9 gene to make maximum coverage, and genotyped them by using RFLP-PCR and ligase detection reaction (LDR) methods to test its associations among 151 NSOCs (53 NSCLP, 52 NSCLO and 46 NSCPO) from Western Han Chinese population. RESULTS: Allelic TDT results showed that G allele at rs12941170 of SOX9 was under-transmitted among NSOCs (p=0.00014, OR=0.55 and 95%CI: 0.40-0.75), which could indicate that the G allele is protective against NSOCs; parent-of-origin effect analysis showed that G allele at rs12941170 was maternally under-transmitted (p=0.002), while there was no statistically difference between the maternal and paternal transmission of it. To test if the adjacent SNPs travel together from parents to the affected individual, we carried out the sliding window haplotype analysis, it is interesting to find that the haplotypes carrying the G allele at rs12941170 also was under-transmitted for NSOCs, NSCL/P, NSCLP and NSCPO (lowest p=0.00033). CONCLUSIONS: This study suggested that G allele at rs12941170 was protective, which could decrease the risk for NSOCs from Western Han Chinese population, and it will provide new reference for future research and genetic counseling in NSOCs.
Authors: Renato Assis Machado; Hercílio Martelli-Junior; Silvia Regina de Almeida Reis; Erika Calvano Küchler; Rafaela Scariot; Lucimara Teixeira das Neves; Ricardo D Coletta Journal: Front Cell Dev Biol Date: 2021-07-08