NTN1 gene was risk to non‐syndromic cleft lip only among Han Chinese population

Abstract

Objective Genome‐wide association studies (GWAS) found NTN1, NOG and the region between CREBBP and ADCY9 were risks to non‐syndromic cleft lip with or without cleft palate (NSCL/P). However, the association of single nucleotide polymorphisms (SNPs) in these genes with NSCL/P in Western China is unknown. Subjects and Methods We selected seven SNPs in NTN1, NOG and between CREBBP and ADCY9, and then performed transmission disequilibrium test (TDT), parent‐of‐origin effect and sliding window haplotype analysis to test the associations among 302 NSCL/P case–parent trios from Western Han Chinese. Results We found allele G at rs4791774 in NTN1 was significantly overtransmitted among non‐syndromic cleft lip only (NSCLO) (p = 0.0067, OR = 1.79, 95% CI: 1.17–2.74); rs4791774 and rs9915089 tightly linked with each other among NSCL/P (D′ = 0.87, r2 = 0.67) and haplotypes carrying the risk allele G at rs4791774 were always found to be overtransmitted from parents to cases. Motif analysis indicated that allele G at rs4791774 could greatly alter the affinity of Myc_disc7, so allele G at rs4791774 in NTN1 might modulate C‐MYC transcription to participate in the aetiology of NSCLO. Conclusions Our study suggested allele G at rs4791774 in NTN1 gene is risk of NSCLO, which could greatly increase the risk to have a baby with cleft.

Genetics and signaling mechanisms of orofacial clefts

“…The extracellular matrix (ECM) plays many important roles in the tissue movements that occur during craniofacial morphogenesis, and as such its function is intimately linked with OFCs. The mechanisms by which ECM activity contributes to OFCs is discussed in greater detail within a companion review article (Ji et al, 2020), though several genes involved in ECM regulation have been linked to NSCL/P, including the laminin‐related netrin 1 ( NTN1 ), implicated by both genome‐wide and targeted studies (Beaty et al, 2010; Beaty et al, 2013; Q. Guo et al, 2017; S. Jiang et al, 2019; E. J. Leslie, Carlson, et al, 2016; E. J. Leslie, Liu, et al, 2016; Y. Yu et al, 2017). Other ECM regulatory molecule genes for which possible association with nonsyndromic OFCs have been found include those encoding the ECM remodeling proteins matrix metalloproteinase 3 and 16 ( MMP3/16 ) (Kumari, Singh, & Raman, 2018; Y. Yu et al, 2017), tissue inhibitor of metalloproteinase 2 ( TIMP2 ) (Nikopensius et al, 2011), and ADAM Metallopeptidase with thrombospondin type 1 motif 20 ( ADAMTS20 ) (Wolf et al, 2015).…”

Exploring the Molecular Mechanism of lncRNA–miRNA–mRNA Networks in Non-Syndromic Cleft Lip with or without Cleft Palate

“… 34 Elsewhere, a study confirmed that rs4791774 in NTN1 could regulate c-Myc transcription and contributed to the etiology of non-syndromic cleft lip only (NSCLO). 35 Numerous reports have further confirmed the close association between the 8q24 chromosome region (where the c-Myc gene is located) and NSCLP, which can be ascribed to the variants of the tissue-specific enhancer of c-Myc or other genes. 36–38 Here, qPCR analysis of clinical samples showed significantly lower expression of c-myc in the NSCL/P group as compared to that, of the control group.…”

Investigação do histórico familial entre sujeitos com diferentes tipos de fissuras orofaciais não sindrômicas

“…Cerca de 30% a 40% dos casos se enquadram nas fissuras sindrômicas, e existem mais de 300 síndromes descritas nas quais a fissura labiopalatina pode fazer parte do fenótipo, incluindo desordens cromossômicas e mendelianas (AQUINO et al, 2011;MENG et al, 2009;SCAPOLI et al, 2008 (JIA et al, 2017;KHAN et al, 2018;ZHANG et al, 2018;JIANG et al, 2019;NEVES et al, 2019).…”