Association Between Rs1805087 Polymorphisms Of MTR Gene And Non-syndromic Cleft Lip With Or Without Cleft Palate

NSCL/P (non-syndromic cleft lip with or without cleft palate, NSCL/P) is a common congenital maxillofacial deformity, and its incidence varies from country to country, region, race, Asians are the easier to have such disease than the people in Europe and other ethnics. The incidence is about 1.30/1000 in China. NSCL/P not only results in the maxillofacial deformities, but also affects patients'hearing, sound, physical and mental health, creating a heavy burden on family and society, and affecting the quality of the population. Now NSCL/P is considered a complex disease,and molecular biology studies suggest that many genes are related to NSCL/P.Folic acid is a water-soluble B vitamins, and is also a compound made up of the aminoglutaminic acid and pterin acid. After absorbed in the intestine, Folic acid goes into the liver by the way of the portal vein. In the liver under the action of dihydrofolate reductase, Folic acid turns into tetrahydrofolic acid. In the body, tetrahydrofolic acid get involved in synthesis and transformation of purine and pyrimidine nucleotide. Folate metabolic pathway is essential in the maintenance DNA methylation and de novo DNA synthesis and DNA repair. If the key enzyme of folate metabolism gene mutation, its activity will change significantly. It affects DNA methylation and lead to chromosomal aberrations. Studies have shown that folate supplementation during pregnancy can reduce the incidence of cleft lip and palate 50%.The 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) gene, located in chromosome 1q43, which encodes 1265 amino acids. MTR encodes the enzyme 5-methyltetrahydrofolate-homocysteine methyltransferase. This enzyme, also known as cobalamin-dependent methionine synthase, catalyzes the final step in methionine biosynthesis, catalyzing the remethylation of homocysteine to methionine. The gene rs1805087 (2756A> G) polymorphism of MTR ,which results in the substitution of the amino acid, aspartic acid, with glycine in codon 919 of the protein, causing the abnormal of S-adenosyl methionine (SAM) levels in intracellular, affecting the DNA methylation.We detected the association of the SNPs gene locus rs1805087 polymorphisms of MTR gene and non-syndromic cleft lip with or without cleft palate, by 174 NSCL/P patients and 169 controls.0bjective To investigate the association of the rs1805087 polymorphisms of MTR gene with NSCL/P in Shanxi province,China.Methods The rs1805087 polymorphisms of MTR gene was examined by PCR-RFLP in both 174 patients and the 169 controls in Shanxi province,China. Hardy-Weinberg equilibrium is tested by Pearsonχ2. Genotype and allele frequencies were analysed by SPSS15.0.At the same time , the value of the the Odds ratios, (OR) and 95% confidence interval (95% CI) was estimated.Results The genotypic distribution of rs1805087 was not deviated from the Hardy-Weinberg Equilibrium. The was no statistical difference in genotype and allele frequencies for MTR rs1805087 variants between patients and healthy individuals(P>0.05). The was no statistical difference in allele frequencies for MTR rs1805087 variants between clinical phenotypes with NSCL/P and healthy individuals.One homozygous mutant genotype GG is found.Conclusion The rs1805087 polymorphism of MTR gene was not associated with NSCL/P in Shanxi province,China.In the CLP group, the frequency of G allele is higher,and the allele may play a role in the disease.