Transmission analysis of TGFB1 gene polymorphisms in non-syndromic cleft lip with or without cleft palate. (September 2017)

• Record Type: Journal Article
• Authors: Raju, Ginila T.; Lakkakula, Bhaskar V.K.S.; Murthy, Jyotsna; Kannan, Munirajan Arasambattu; Paul, Solomon F.D.
• Is Part Of: International journal of pediatric otorhinolaryngology. Volume 100(2017:Sep.)
• Page Start: 14
• Page End: 17
• Publication Date: 2017-09
• Subjects: TGFB1, SNP -- Haplotype -- TDT and NSCL/P; Otolaryngology -- Periodicals; Pediatrics -- Periodicals; Otolaryngology -- Periodicals; Pediatrics -- Periodicals; Oto-rhino-laryngologie -- Périodiques; Pédiatrie -- Périodiques; 618.9209751
• DOI: 10.1016/j.ijporl.2017.06.015
• Languages: English
• ISSNs: 0165-5876

Abstract

Abstract: Objectives: Transforming growth factor beta1 (TGF-β1) plays a significant role in craniofacial development. Previous linkage studies reported that the TGF-β1-locus at 19q13.1 harbour predisposing genes for non-syndromic oral clefts. In the present study case parents triads were evaluated to find the transmission effects of genetic variants in TGF- β1 towards non-syndromic cleft lip or palate (NSCL/P). Methods: Using allelic discrimination method148 families (case-parent triads) were assessed for single nucleotide polymorphisms (SNPs) in TGF-β1 gene. The SNPs were checked for mendelian errors and Hardy-Weinberg equilibrium (HWE). Transmission disequilibrium test and haplotype frequencies were estimated. Results: The TGF-β1 SNPs showed very low minor allele frequencies (MAFs) and observed heterozygosity (Hobs). The transmission disequilibrium test (TDT) and parent-of-origin likelihood ratio tests (PO-LRT) were not significant for any of the SNPs tested. Strong linkage disequilibrium (r 2 = 0.722) was found between rs1800469 and rs1800470 SNPs. Haplotype analysis ignoring parent of origin showed strong evidence of excess transmission but it is not significant (p-value = 0.293). Conclusion: Transmission of minor alleles were not observed from either parent indicating that the TGF-β1 gene polymorphisms by themselves do not confer risk for non-syndromic oral clefts but, rather, modify the stability and the activation process of TGF-β1. As the number of families included in the study are less, results must be considered still preliminary and require replication using more families.