title: Transforming growth factor-beta3 gene SfaN1 polymorphism in Korean nonsyndromic cleft lip and palate patients.
abstract: The nonsyndromic cleft lip and palate (NSCL/P) is a congenital deformity of multifactorial origin with a relatively high incidence in the oriental population. Various etiologic candidate genes have been reported with conflicting results, according to race and analysis methods. Recently, the ablation of the TGF-beta3 gene function induced cleft palates in experimental animals. Also, polymorphisms in the TGF-beta3 gene have been studied in different races; however, they have not been studied in Koreans. A novel A --> G single nucleotide polymorphism (defined by the endonuclease SfaN1) was identified in intron 5 of TGF-beta3 (IVS5+104 A > G). It resulted in different genotypes, AA, AG, and GG. The objective of this study was to investigate the relationship between the SfaN1 polymorphism in TGF-beta3 and the risk of NSCL/P in the Korean population. The population of this study consisted of 28 NSCL/P patients and 41 healthy controls. The distribution of the SfaN1 genotypes was different between the cases and controls. The frequency of the G allele was significantly associated with the increased risk of NSCL/P [odds ratio (OR) = 15.92, 95% confidence interval (CI) = 6.3-41.0]. The risk for the disease increased as the G allele numbers increased (GA genotype: OR = 2.11, 95% CI = 0.38-11.68; GG genotype: OR = 110.2, 95% CI = 10.67 - 2783.29) in NSCL/P. A stratified study in patients revealed that the SfaN1 site IVS5+104A > G substitution was strongly associated with an increased risk of NSCL/P in males (p < 0.001), but not in females. In conclusion, the polymorphism of the SfaN1 site in TGF-beta3 was significantly different between the NSCL/P patients and the control. This may be a good screening marker for NSCL/P patients among Koreans.
authors.affiliation: Department of Orthodontics, College of Dentistry, Seoul National University, Seoul, Korea.
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Kim
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Je-Yong
authors.initials: JY
authors.lastname: Choi
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Nahm
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism*; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D011110:Polymorphism, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053782:Transforming Growth Factor beta3
chemical_list: D017931:DNA Primers; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D015252:Deoxyribonucleases, Type II Site-Specific; C065993:endodeoxyribonuclease SfaNI