title: MTHFR, TGFB3, and TGFA polymorphisms and their association with the risk of non-syndromic cleft lip and cleft palate in China.
abstract: Our previous results indicated a moderate association between the methylenetetrahydrofolate reductase (MTHFR) gene 677C-T variant and an increased risk of non-syndromic cleft lip with or without cleft palate (nsCL/P) among the northern but not southern population in China, suggesting possible genetic heterogeneity in the etiology of nsCL/P between these two populations. It remains unknown whether the transforming growth factor alpha (TGFA) gene TaqI polymorphism and transforming growth factor beta 3 (TGFB3) gene CA repeats influence the risk of nsCL/P differently between the northern and southern Chinese populations. In this study of 188 Chinese case-parent triads, we found an independent association between the TGFB3 variant and risk of nsCL/P (OR = 2.10, 95% CI: 1.25-3.54 for heterozygotes; OR = 1.78, 95% CI: 0.83-3.83 for homozygotes). The MTHFR variant was associated with an increased risk of nsCL/P among children in the north (OR = 3.11, 95% CI: 1.18-8.23 for heterozygotes; OR = 3.36, 95%CI: 1.14-9.93 for homozygotes) and appear to interact marginally with the TGFB3 variant in the occurrence of nsCL/P among southern subjects (OR = 0.26, 95% CI: 0.06-1.07). No association was found between the TGFA variant and risk of nsCL/P in our data. Our results suggest that the TGFB3 gene variant may be an important genetic risk factor for nsCL/P occurrence in Chinese children, and we found no evidence of heterogeneity between northern and southern Chinese populations in the associations between TGFB3 and TGFA variants and risk of nsCL/P, but these results warrant further investigation.
authors.affiliation: National Reference Laboratory on Reproductive and Child Health, Ministry of Health, Peking University Health Science Center, Beijing, China.
authors.forename: JiangHui
authors.initials: J
authors.lastname: Zhu
authors.forename: Ling
authors.initials: L
authors.lastname: Hao
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Bailey
authors.forename: Yihua
authors.initials: Y
authors.lastname: Tian
authors.forename: Zhu
authors.initials: Z
authors.lastname: Li
mesh_terms: D002681:China; D002971:Cleft Lip / Q000175:diagnosis / Q000235:genetics*; D002972:Cleft Palate / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012306:Risk; D016211:Transforming Growth Factor alpha / Q000235:genetics*; D053782:Transforming Growth Factor beta3 / Q000235:genetics*
chemical_list: C509044:TGFB3 protein, human; D016211:Transforming Growth Factor alpha; D053782:Transforming Growth Factor beta3; D042965:Methylenetetrahydrofolate Reductase (NADPH2)