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Genetic Polymorphisms Of CCR5, CCR2 And CX3CR1 Of HIV Coreceptor In Uygur Population Of Xinjiang And Yi Population Of Sichuan In China

Posted on:2005-03-31Degree:MasterType:Thesis
Country:ChinaCandidate:X L DengFull Text:PDF
GTID:2144360125462597Subject:Biochemistry and Molecular Biology
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Genetic polymorphisms of HIV co-receptors CCR5, CCR2 and CX3CR1 have been close associated with resistance during HIV-1 infection and diease progression, coreceptors share different genetic polymorphisms in different nationalities. There are more different nationalities appearing different inherent background in China. HIV-1 has high prevalence in Liangshang Yi municipality in Sichuan province and Xinjiang Uygur municipality, where Yi and Uygur minority groups are concentrated respectively. We investigated the differencies of genetic polymorphisms of those three coreceptors in the two minorities, at the same time, analyzed thoses differencies' role in HIV infection and AIDS progression. Our work might be acting as basic work for further study on the epidemic feature, HIV pathogenesis, genetic resistance and therapeutic vaccine in different nationalities.Methods: To Yi group, Blood samples were collected from 119 HIV seronegative and 88 HIV-1 seropositive individuals; To Uygur group, 125 HIV seronegative and 174 HIV-1 seropositive samples were collected. Gene polymorphisms were measured by PCR (polymerase chain reaction), PCR-RFLP (PCR-restriction fragment length polymorphism-based), clone and gene sequencing methods.Results: To Yi group, 2 heterozygotes (CCR5-wt/ 32) and none homozygote (CCR5-32/ 32) were observed in 119 healthy individuals, allelic frequency was 0.84%; No mutant was found in 88 HIV-1 infected individuals. At CCR2 locus, 26 heterozygotes (CCR2-64V/64I) and two homozygotes (CCR2-64I/64I) were observed in healthy individuals, theallelic frequency was 12.61%; in infected individuals, 12 heterozygotes and 7 homozygotes were observed, the allelic frequency was 14.77%. The allelic frequencies of CX3CR1-V249I were 15.7% and 12.6% in normal and positive samples, respectively; the allelic frequencies of CX3CR1-T280M were 10.5% and 11.5% in normal and positive samples, respectively; only three haplotypes of CX3CR1 were detected: V249T280, I249T280 and I249M280, the frequencies of the three haplotypes in seronegative and seropositive samples were 91.7%, 2. 6%, 5.7% and 92.5%, 1.7%, 5.8%, respectively.To Uygur group, 9 heterozygotes and none homozygote of CCR5 A 32 were observed in 125 healthy individuals, allelic frequency was 3.6%; 14 heterozygotes and none homozygote were found in 174 HIV-1 infected individuals, allelic frequency was 4. 02%. At CCR2 locus, 16 heterozygotes (CCR2-64V/64T) and 4 homozygotes (CCR2-64I/64I) were observed in 108 healthy individuals, the allelic frequency was 11.1%; in 148 infected individuals, 23 heterozygotes and 4 homozygotes were observed, the allelic frequency was 10. 47%. Only CX3CR1-V249I was observed in 125 normal and 174 postive samples. The allelic frequencies of CX3CR1-V249I were 38.4% in normal and 31.6% in positive samples; only two haplotypes of CX3CR1 were detected: V249T280 and I249T280, the frequencies of the two hapiotypes in seronegative and seropositive samples were 80%, 20% and 83%, 17%, respectively.Statistical analysis: The statistical analysis showed that the differences of three loci between healthy and infected individuals in two enthic groups were insignificant. Conclusion:1. There are different genetic polymorphisms in different nationalities; it is valuable to study those polymorphisms in different nationalities.2. This study investigated the genetic polymorphisms of HIVcoreceptor in Yi ethnic group of Sichuan and Uygur of Xinjiang by case-control study for the first time. It would be added up to the genetic background information in China. Our results would be used to explore the origin of those coreceptors by combining with other groups' resultS.3. Our results would be used for evaluating the groups' hereditary susceptibility to HIV-1 infection. Our work might be acting as basic work for further study on the epidemic feature, HIV pathogenesis, genetic resistance and therapeutic vaccine in different nationalities in China.
Keywords/Search Tags:Allelic gene, Coreceptor, Genetic polymorphism, HIV-1, Uygur ethnic group, Yi ethnic group
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