Preliminary Study Of Their Relationship Between Msx2,SLUG,HOXD4 And Neural Tube Defects

Objective: To study the relationship between the genetic mutations of Msx2A59G, Msx2C386T,SLUGC1548A and neural tube defects in the people of Han nationality of Shanxi in China.Screen differentially expressed genes of neural tube defects (NTDs) by cDNA microarray technique among the population of Shanxi Lvliang. Classify the target genes to different pathways, such as metabolism, gene translation regulator, signaling, apoptosis and so on. Select the HOXD4 gene to study further to clarify the mechanism of neural tube defects.Method: Determination of the Msx2A59G, Msx2C386T gene mutation and the SLUGC1548A gene mutation by ARMS method in 39 patients with neural tube defects and 32 normal people for control.Using high-throughput genechip technology to analysis the expression pattern of NTDs. All these target genes were classified to different pathways, such as metabolism, gene translation regulator, signaling, apoptosis and so on. We select the HOXD4 as our target gene. RT-PCR method were also chosen to test the change of HOXD4 in NTDs embryos of different weeks.Result: The frequency of Msx2 59 allele G homogenetic type and G allele (20.5% and 43.6%) in NTDs group was higher than those in control group (12.4% and 35.9%). The frequency of Msx2 386 allele T homogenetic type and T allele (23.0% and 46.8%) in NTDs group was higher than those in control group (9.4% and 25.0%). The frequency of SLUG A homogenelic type and A allele (25.6%和35.1%) in NTDs was higher than those in control group (6.3%和27.3%). Logistic Regression analysis showed that together with the T allele in Msx2 and the A allele in SLUG were related to neural tube defects (p<0.05), The odds ratios (OR) of the T allele in Msx2C386T and the A allele in SLUGC1548A were 2.756 (95%CI 1.269-5.978) and 3.610(95%Cl 1.547-8.425) respectively.we obtain 22209 differentially expressed transcripts to human NTDs. There were 74 genes over-expressed about 2 times ,they were 3 genes of oxidative phosphorylation,7genes of zinc finger,2 genes of glutathione metabolism,2 genes of eicosanoid synthesis,4 genes of matrix metalloproteinases, 6 genes of G protein signaling pathway, and there were 387 genes low-expressed about 2 times ,they were 8 genes of DNA replication and nucleotide metabolism,7 genes of inflammatory response pathway, 6 genes of apoptosis,2 genes of Integrin-mediated cell adhesion,4 genes of citrate cycle, 9 genes of G protein signaling pathway and so on. HOXD4 is our target gene, it shows over-expression about 20.9times.The RT-PCR(p<0.01) also show the same results.Conclusion: Genetic mutations of Msx2A59G, Msx2C386T and SLUGC1548A are found in the people of Han nationality of Shanxi in China. We confirm that the Genetic mutations of...