The Relationship Between ACP1Genetic Polymorphism And Coronary Heart Disease&Cancers In Chinese Population

Tyrosine phosphorylation is a fundamental mechanism for numerous importantaspects of eukaryote physiology, as well as human health and disease. Compared toprotein phosphorylation in general, phosphorylation on tyrosine is extensively utilizedonly in multicellular eukaryotes. Tyrosine phosphorylation is used for communicationbetween and within cells, the shape and motility of cells, decisions to proliferateversus differentiate, cellular processes like regulation of gene transcription, mRNAprocessing, and transport of molecules in or out of cells. Tyrosine phosphorylationalso plays an important role in the coordination of these processes among neighboringcells in embryogenesis, organ development, tissue homeostasis, and the immunesystem. Abnormalities in tyrosine phosphorylation play a role in the pathogenesis ofnumerous inherited or acquired human diseases from cancer to immune deficiencies.Although the human ACP1can dephosphorylate a number of tyrosine kinases andtheir substrates, its physiological function is still unclear. The preservation of a class IIPTP through evolution to humans and the correlation of allelic variants of ACP1withmany common human diseases, such as rheumatoid arthritis, asthma, diabetes,cardiomyopathy, and Alzheimer’s disease, indicate that ACP1likely is involved in theregulation of one or several fundamental processes in cell physiology.We collected over600blood samples from patients with Coronary Heart Diseasesand cancers, extracted genomic DNA from the whole blood and determined the ACP1genotypes with polymerase chain reaction restriction fragment length polymorphism(PCR–RFLP). The C-T transition at exon3and the A-G transition at exon5generatea Hha I and a Taq I restriction site, respectively. A382-bp segment spanning the entireexons3F and3S was amplified. A320-bp segment including exon5was amplifiedusing corresponding primers. The382-bp exon3amplicon was fully cleaved by Hha Iand then electrophoresed on3%agarose gels. The digestion created two fragments of240and142bp for the ACP1*A and ACP1*B alleles, whereas the ACP1*C allele wasnot cut. Similarly, the320-bp PCR product was digested by Taq I, generating twofragments of101and219bp for the ACP1*A allele, but not for the*B and*C alleles. According to the patterns of electrophoresis，the genotypes can be verified. Then weanalyzed the distribution of genotypes separately among females and males.Statistical results showed that ACP1genotype and allele distributions in femalesubjects with CHD differed significantly from that of healthy females due to adeficiency of AB genotype. No significant difference was observed in CHD malescompared to controls. An odds ratio analysis is presented to proved female carriers ofAB genotype are protected from CHD. No significant pattern is observed in males. Inpatients with lung cancers, breast cancers and cervical cancers, there was nosignificant relevance with controls in ACP1genotype and allele distributions both infemales and males. It is worthwhile to note that in patients with esophageal carcinoma,the allele distribution is prominently different from that of controls, the A allele is astrong risky factor of pathogenesis, whereas the B allele carriers are much lesssusceptive to esophageal carcinoma.The association between ACP1genetic polymorphism and susceptibility todiseases highlights a reliable direction of ACP1functional exploration for us, thesignificant relationship with certain diseases could suggest the possible physiologicalprocesses involved ACP1and the possible way of regulation, which also provide us anovel therapeutic target of heart diseases and cancers.