Association Study Of DAT And NET Gene Polymorphisms In Urgur Traditional Medicine Sydrome Of Breast Cancer And Other Cancer

The Uighur medicine has been thinking highly of the uniformity and integrality of the organism and the relationship to the nature, and it considers that various tissues and systems in the human body are inalienable in structure and function.The Uighur medicine has its own unique theories and treatment methods for complex diseases. The fluid theory in Uighur medicine describes the following:body fluid is the basic matter during the vital life and physiological activity; it is produced and utilized continuously and provides the energy for the vital activity. The body fluid keeps the correspondence balance, inter-restriction and complementation.Uighur medicine has annotation to the pathogenesis and clinical manifestation of cancer, and pose that different syndrome has distinct prevention and treatment.The abnormal Savda Hilit syndrome as the final pathological production of Balgham Hilit, Sapra Hilit, Qan Hilit is related closely to the cancer.The human DAT1 gene encodes for a dopamine transporter and regulates the re-uptake of released dopamine back into presynaptic terminals after its synaptic release. The human dopamine transporter gene(DATl),located on chromosome 5p15.3,contains a variable number tandem repeat(VNTR)in its 3'-untranslated region due to repetition of a 40-bp core sequence,ranging from 3 to 13 times depending on the population studied.However,two alleles containing the 9-and 10-repeats were the most common alleles in most studies,while the remaining ones were rare and also often geographically restricted.The VNTR polymorphism in the DAT1 gene is not silent but affects the expression of this gene yielding increased levels of mRNA,especially with the 10-repeats allele. NET recaptures as much as 90% of released NE making it a critical mediator of NE inactivation and presynaptic catecholamine homeostasis.Thus, NET plays a role in controlling the intensity and duration of signal transduction.The gene coding for norepinephrine transporter (NET) is located on chromosome 16q12.2 and spans approximately 45 kb containing 14 exons.Since the 5'region of the NET gene has been suggested to play a pivotal role in transcription regulation.Fajas et al pointed out that SNP T/C(rs2242446) may be influence transcription.Here our study have three part.PartⅠRelationship between genetic polymorphisms of DAT1 VNTR Region and cancer with abnormal HilitObjective:This study was to investigate the relationship between the 40bp VNTR polymorphism of dopamine transportergene(DATl) and cancer with Uighur medicine abnormal Hilit on Chinese Uighur population of Xinjiang. Methods: Divided the caner patients into four body fluids according to Uighur medicine theory, the polymerase chain reaction and VNTR polymorphism technique was employed to detect genotype and allele frequencies of a 40 bp VNTR polymorphism situated in 3'untranslated region of the DAT1 gene in 47 cancer patients with abnormal black Savda,26 caner patients with other abnormal Hilit and 57 normal control subjects in Uighur population of Xinjiang province. Results:(1)In our sample,the repeat numbers of 40 bp were 6 to 11(PCR product length of 320 bp to 520 bp)and 10-repeats allele(480 bp)detected was the dominant allele of DATl gene polymorphisms with the allele frequency 90.4%.Six kinds of genotype were detected in this study and the genotype 480 bp/480 bp was the most common genotype with genotype frequency 80.7%.(2) The susceptibility to caner patients with abnormal black Savda among the subjects with 10 repeat(R)allele and 10/10 genotypes and the subjects with non-10 repeat(R)allele and non-10/10 genotypes were similar(P=0.158;P=0.138).No significant differences for the genotype frequency or the allele frequency of the 40bp VNTR polymorphism of DAT1 were revealed between caner patients with abnormal black Savda and caner patients with other abnormal Hilit(P=0.729;P=0.782) Conclusion:The 40bp VNTR polymorphism of DATl may not be correlated to the susceptibility to cancer with Uighur medicine abnormal Hilit.PartⅡAssociation analysis between polymorphism of dopamine transporter variable number tandem repeat and breast cancer with abnormal HilitObjective:To explore the association between polymorphism of dopaminel transporter variable number tandem repeat(DAT1 VNTR) and breast cancer with abnormal Hilit in Chinese Han population from Xinjiang. Methods:Divided the breast caner patients into four body fluids according to Uighur medicine theory, the polymerase chain reaction and VNTR polymorphism technique was employed to detect genotype and allele frequencies of a 40 bp VNTR polymorphism situated in 3'untranslated region of the DAT1 gene in 144 breast cancer patients with abnormal Hilit and 104 normal control subjects in han population of Xinjiang province. Results: (1)In our sample,the repeat numbers of 40 bp were 7 and 9 to 11(PCR product length of 360 bp and 440 bp to 520 bp)and 10-repeats allele(480 bp)detected was the dominant allele of DATl gene polymorphisms with the allele frequency 90.9%;Seven kinds of genotype were detected in this study and the genotype 10/10 was the most common genotype with genotype frequency 83.1%.(2)The frequency of 10-repeats allele and 10/10 genotype was significantly higher in the breast caner patients with abnormal balgham Hilit than in the control(OR=0.127,95%CI为0.016-0.988, P=0.026;OR=0.134,95%CI为0.018-1.016,P=0.020) and breast caner patients with abnormal Sapra Hilit(OR=0.132,95%CI为0.016-1.075,P=0.049;OR=0.132, 95% CI为0.017-1.042,P=0.033).Conclusion:The 10-repeats allele and 10/10 genotype of the 40bp VNTR polymorphism of DAT1 may increase risk of breast cancer with Uighur medicine abnormal balgham Hilit in Chinese Han population from Xinjiang and may not be correlated to the susceptibility to breast cancer with Uighur medicine abnormal Sapra Hilit.PartⅢNorepinephrine transporter gene polymorphism T-182C is not associated with breast cancer with abnormal HilitObjective:This study was to investigate the relationship between the polymorphisms of T-182C (rs2242446) in NET gene and breast cancer with abnormal Hilit in Chinese Han population from Xinjiang. Methods:Divided the breast caner patients into four body fluids according to Uighur medicine theory, the polymerase chain reaction and VNTR polymorphism technique was employed to detect genotype and allele frequencies of the T-182C polymorphism situated in NET gene in 126 breast cancer patients with abnormal Hilit and 90 normal control subjects in han population of Xinjiang. Results:(1)No significant differences in genotype and allele frequencies of the polymorphisms of T-182C in NET gene were found between controls and total breast cancer(P=0.249;P=0.152)or between breast cancer patients with abnormal Hilit and controls(P>0.05).(2)No significant differences for the genotype frequency or the allele frequency of the polymorphisms of T-182C in NET gene were revealed between breast caner patients with abnormal black Savda and breast caner patients with other abnormal Hilit(P>0.05).Conclusion:The polymorphisms of T-182C in NET gene are not major risk factors in increasing susceptibility to either breast cancer or breast cancer patients with abnormal Hilit in Chinese Han population from Xinjiang.