[Association study between candidate genes on transforming growth factor-ß signaling pathway and the risk of non-syndromic cleft lip with or without cleft palate in Chinese populations].

OBJECTIVE: To explore the association between 10 candidate genes on transforming growth factor-ß (TGFB) signaling pathway and non-syndromic cleft lip with or without cleft palate (NSCL/P) among Chinese populations, and to study the gene-environment interaction. METHODS: A total of 806 Chinese Han NSCL/P trios were ascertained from an international consortium, which conducted a genome-wide association study using a case-parent trio design to investigate the genes affecting risk to NSCL/P. The transmission disequilibrium test (TDT) was used to test for effects of 343 single nucleotide polymorphisms (SNPs) in 10 genes on TGFB signaling pathway including DCN, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, BAMBI, SMAD2, SMAD3 and SMAD4. The conditional regression models were used to test for gene-environment interaction. RESULTS: For TDT, although 19 SNPs showed nominal significant association with NSCL/P, no significant evidence of association was seen for all SNPs in 806 NSCL/P trios after Bonferroni correction. The interactions between genes and maternal smoking, environmental tobacco smoke, alcohol consumption and multi-vitamin supplementation during pregnancy did not attain statistical significance after correction for multiple comparisons. CONCLUSION: No evidence for SNP effect of genes on TGFB signaling pathway and significant gene-environment interaction was seen in our data.

Apoptosis induction by Epican Forte in HTLV-1 positive and negative malignant T-cells.

The effects of a novel nutrient formulation Epican Forte (EF) were evaluated on proliferation and induction of apoptosis using non-cytotoxic concentrations against HTLV-1 positive (HuT-102 & C91-PL) and negative (CEM & Jurkat) cells. EF showed anti-proliferative effect as determined by MTT assay and TGF mRNA protein expression using RT-PCR. EF resulted in the down-regulation of TGF-alpha and an up-regulation in TGF-beta2. EF caused a significant increase in apoptotic cells in the preG1 phase. These results were confirmed using Cell Death ELISA and Annexin V-FITC. Induction of apoptosis was caused by an up-regulation of p53, p21 and Bax protein levels and a down-regulation of Bcl-2alpha protein expression level.

The Drosophila p38 MAPK pathway is required during oogenesis for egg asymmetric development.

In mammalian cells, the p38 mitogen-activated protein kinase (MAPK) pathway is activated in response to a variety of environmental stresses and inflammatory stimuli. However, the role of p38 MAPK signaling in unchallenged conditions remains largely unknown. We have isolated mutations in a Drosophila p38 MAPKK gene homolog, licorne (lic), and show that during oogenesis, lic is required in the germ line for correct asymmetric development of the egg. In lic mutant egg chambers, oskar mRNA posterior localization is not properly maintained, resulting in anteroposterior patterning defects in the embryo. Furthermore, lic loss-of-function in the germ line leads to reduced EGF receptor activity in dorsal follicle cells and ventralization of the egg shell. Both these defects are associated with a diminution of gurken protein levels in the oocyte. Our phenotypic data argue for a role of lic in a post-transcriptional regulation of the grk gene. Furthermore, they show that in addition to the well-characterized Ras/Raf/ERK MAPK pathway acting in the follicle cells, another related signaling cascade, the p38 MAPK pathway, is required in the germ line for correct axes determination. These results provide the first genetic demonstration of an essential function for a p38 pathway during development.