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Journal of Peking University(Health Sciences) >

2024 , Vol. 56 >Issue 3: 384 - 389

DOI: https://doi.org/10.19723/j.issn.1671-167X.2024.03.002

Gene-gene/gene-environment interaction of transforming growth factor-β signaling pathway and the risk of non-syndromic oral clefts

  • Tianjiao HOU ,
  • Zhibo ZHOU ,
  • Zhuqing WANG ,
  • Mengying WANG ,
  • Siyue WANG ,
  • Hexiang PENG ,
  • Huangda GUO ,
  • Yixin LI ,
  • Hanyu ZHANG ,
  • Xueying QIN ,
  • Yiqun WU ,
  • Hongchen ZHENG ,
  • Jing LI ,
  • Tao WU ,
  • Hongping ZHU
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  • 1. Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China
    2. Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China
    3. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, NHC Research Center of Engineering and Technology for Computerized Dentistry, NMPA Key Laboratory for Dental Materials, Beijing 100081, China
    4. Department of Nutrition and Food Hygiene, Peking University School of Public Health, Beijing 100191, China
    5. Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, NHC Research Center of Engineering and Technology for Computerized Dentistry, NMPA Key Laboratory for Dental Materials, Beijing 100081, China

Received date: 2024-02-18

  Online published: 2024-06-12

Supported by

Supported by the National Natural Science Foundation of China(81573225)

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Abstract

Objective: To explore the association between polymorphisms of transforming growth factor-β (TGF-β) signaling pathway and non-syndromic cleft lip with or without cleft palate (NSCL/P) among Asian populations, while considering gene-gene interaction and gene-environment interaction. Methods: A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium, which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P. After stringent quality control measures, 343 single nucleotide polymorphism (SNP) spanning across 10 pivotal genes in the TGF-β signaling pathway were selected from the original genome-wide association study(GWAS) dataset for further analysis. The transmission disequilibrium test (TDT) was used to test for SNP effects. The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction. Environmental factors collected for the study included smoking during pregnancy, passive smoking during pregnancy, alcohol intake during pregnancy, and vitamin use during pregnancy. Due to the low rates of exposure to smoking during pregnancy and alcohol consumption during pregnancy (<3%), only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed. The threshold for statistical significance was rigorously set at P =1.46×10-4, applying Bonferroni correction to account for multiple testing. Results: A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P (P<0.05), but none of these associations was statistically significant after Bonferroni' s multiple test correction. However, there were 6 pairs of SNPs rs4939874 (SMAD2) and rs1864615 (TGFBR2), rs2796813 (TGFB2) and rs2132298 (TGFBR2), rs4147358 (SMAD3) and rs1346907 (TGFBR2), rs4939874 (SMAD2) and rs1019855 (TGFBR2), rs4939874 (SMAD2) and rs12490466 (TGFBR2), rs2009112 (TGFB2) and rs4075748 (TGFBR2) showed statistically significant SNP-SNP interaction (P<1.46×10-4). In contrast, the analysis of gene-environment interactions did not yield any significant results after being corrected by multiple testing. Conclusion: The comprehensive evaluation of SNP associations and interactions within the TGF-β signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations. However, the significant gene-gene interactions identified suggest that the genetic architecture influencing NSCL/P risk may involve interactions between genes within the TGF-β signaling pathway. These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.

Key words： Non-syndromic cleft lip with or without cleft palate; Transforming growth factor-β signaling pathway; Genome-wide association study; Case-parent trio

Cite this article

Tianjiao HOU , Zhibo ZHOU , Zhuqing WANG , Mengying WANG , Siyue WANG , Hexiang PENG , Huangda GUO , Yixin LI , Hanyu ZHANG , Xueying QIN , Yiqun WU , Hongchen ZHENG , Jing LI , Tao WU , Hongping ZHU . Gene-gene/gene-environment interaction of transforming growth factor-β signaling pathway and the risk of non-syndromic oral clefts[J]. Journal of Peking University(Health Sciences), 2024 , 56(3) : 384 -389 . DOI: 10.19723/j.issn.1671-167X.2024.03.002

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