Rs12941170 at SOX9 gene associated with orofacial clefts in Chinese

Jia, Zhong‐Lin; He, Sha; Jiang, Shuyuan; Zhang, Bi-He; Duan, Shijun; Shi, Jiayu; Huang, Ning; Zhu, Wenchao; Shi, Bing

doi:10.1016/j.archoralbio.2016.12.010

Cited by 7 publications

(6 citation statements)

References 37 publications

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“…Many variants across several loci have been associated with NSCL/P in populations of various ancestries (Ingersoll et al, 2010 ; Butali et al, 2014 ; de Araujo et al, 2016 ; Leslie et al, 2016 ; Jia et al, 2017 ; Yu et al, 2017 ). Nineteen of these independent genetic variants have been associated with NSCL/P in genome-wide association studies (GWAS) of European populations.…”

Section: Introductionmentioning

confidence: 99%

Non-syndromic Cleft Lip and Palate Polymorphisms Affect Normal Lip Morphology

2018

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Non-syndromic cleft lip with or without palate (NSCL/P) is a frequent malformation of the facial region. Genetic variants (SNPs) within nineteen loci have been previously associated with NSCL/P in GWAS studies of European individuals. These common variant SNPs may have subtler effects on the morphology of the lip and face in unaffected individuals. Several studies have investigated the genetic influences on facial morphology using land-marking methods, but these landmarks are sparse in the lip region. The aim of this study is to assess for associations between the nineteen NSCL/P SNPs and normal lip phenotypes, using a detailed categorical scale. Three-dimensional laser scanned facial images were obtained of 4,747 subjects recruited from the Avon Longitudinal Study of Parents and Children (ALSPAC) and genetic data was available for 3,643 of them. A polygenetic risk score (PRS) combining the nineteen NSCL/P SNPs was associated with V-shaped Cupid's bow (P = 3 × 10−4) and narrow philtrum (P = 2 × 10−4) phenotypes. Analysis of individual SNPs found strong evidence for association between rs227731 and skeletal II pattern (P = 5 × 10−6). This study finds that known NSCL/P SNPs affect lip phenotypes in the general population, and an increased PRS is associated with narrow philtrum and V-shaped Cupid's bow. However, the difference in NSCL/P PRS between people with and without certain lip features is unlikely to be great enough to serve as a useful marker of NSCL/P risk.

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Section: Introductionmentioning

confidence: 99%

Non-syndromic Cleft Lip and Palate Polymorphisms Affect Normal Lip Morphology

2018

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“…Among genes previously described in association with NSCPO, 38 novel SNPs (except rs2229989 in SOX9 , Jia et al, 2017 ) and 9 novel rare variants were identified in ACACB , CDH1 , COL11A1 , COL11A2 , COL2A1 , CREBBP , FTCD , GRHL3 , JAG2 , LRP6 , MSX1 , MTHFD1 , MTHFR , MTR , OFD1 , POMGNT2 , RFC1 , SHMT1 , SOX9 , TBX1 , TBX22 , TCN2 , TCOF1 , TP63 , and TYMS ( Table 1 ). The biological processes and pathways for these NSCPO-associated genes were generated by STRING ( Table 2 and Supplementary Table 5 ).…”

Section: Resultsmentioning

confidence: 99%

Identification of Novel Variants in Cleft Palate-Associated Genes in Brazilian Patients With Non-syndromic Cleft Palate Only

Machado

Martelli‐Júnior

Reis

et al. 2021

Front. Cell Dev. Biol.

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The identification of genetic risk factors for non-syndromic oral clefts is of great importance for better understanding the biological processes related to this heterogeneous and complex group of diseases. Herein we applied whole-exome sequencing to identify potential variants related to non-syndromic cleft palate only (NSCPO) in the multiethnic Brazilian population. Thirty NSCPO samples and 30 sex- and genetic ancestry-matched healthy controls were pooled (3 pools with 10 samples for each group) and subjected to whole-exome sequencing. After filtering, the functional affects, individually and through interactions, of the selected variants and genes were assessed by bioinformatic analyses. As a group, 399 variants in 216 genes related to palatogenesis/cleft palate, corresponding to 6.43%, were exclusively identified in the NSCPO pools. Among those genes are 99 associated with syndromes displaying cleft palate in their clinical spectrum and 92 previously related to cleft lip palate. The most significantly biological processes and pathways overrepresented in the NSCPO-identified genes were associated with the folic acid metabolism, highlighting the interaction between LDL receptor-related protein 6 (LRP6) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) that interconnect two large networks. This study yields novel data on characterization of specific variants and complex processes and pathways related to NSCPO, including many variants in genes of the folate/homocysteine pathway, and confirms that variants in genes related to syndromic cleft palate and cleft lip-palate may cause NSCPO.

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“…One of effective methods to uncover the genetic etiology of non‐syndromic orofacial cleft (NSOC) is to take casual genes for syndromic orofacial clefts as a target to validate their associations with NSOCs, such as IRF6 and SOX9 (Jia et al, 2017; Zucchero et al, 2004). KCNJ2 gene that locates in 17q23 and encodes Kir2.1 are important regulators of craniofacial development.…”

Section: Discussionmentioning

confidence: 99%

Association analysis of SNPs in GRHL3, FAF1, and KCNJ2 with NSCPO sub‐phenotypes in Han Chinese

et al. 2021

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Objectives Non‐syndromic cleft palate only (NSCPO) is a common congenital deformity with complex etiologies. GRHL3, FAF1, and KCNJ2 have been reported to be involved in the pathogenesis of NSCPO. Up till now, there have been no replication studies based on large Han Chinese. Therefore, this study aimed to investigate associations between GRHL3, FAF1, KCNJ2, and NSCPO sub‐phenotypes patients in Han Chinese. Materials and Methods Firstly, we selected 2 SNPs based on previous literatures: FAF1 (rs3827730) and GRHL3 (rs41268753). Also, we selected 8 tagSNPs in GRHL3 (rs557811, rs609352, rs10903078, rs6659209, rs12401714, rs12568599, rs3887581, rs12024148) and 2 tagSNPs in KCNJ2 (rs75855040 and rs236514). Afterward, we evaluated these SNPs among 1668 NSCPO patients and 1811 normal controls from Han Chinese. Following data were analyzed by PLINK and Haploview program. Results Association analysis under additive model showed that allele A at rs12568599 in GRHL3 gene is significantly associated with NSCPO (p = 0.0034, OR = 1.38 and 95%CI: 1.11–1.72) and its sub‐phenotype incomplete cleft palate (ICP) (p = 0.0039, OR = 1.4 and 95%CI: 1.11–1.75), and it could increase the risk of both NSCPO and ICP. Conclusions This study firstly found that rs12568599 in GRHL3 is associated with NSCPO and ICP in Han Chinese, indicating that sub‐phenotypes of NSCPO have different etiologies.

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Rs12941170 at SOX9 gene associated with orofacial clefts in Chinese

Cited by 7 publications

References 37 publications

Non-syndromic Cleft Lip and Palate Polymorphisms Affect Normal Lip Morphology

Non-syndromic Cleft Lip and Palate Polymorphisms Affect Normal Lip Morphology

Identification of Novel Variants in Cleft Palate-Associated Genes in Brazilian Patients With Non-syndromic Cleft Palate Only

Association analysis of SNPs in GRHL3, FAF1, and KCNJ2 with NSCPO sub‐phenotypes in Han Chinese

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