Study On Relationship Between Polymorphism Of HLA-Ⅱ Genetypes And HPV Infection In Xinjiang Uyghur Women With Cervical Lesions And Cervical Cancer

Objective: To investigate the relationships between in the carcinogenesis OF HLA-DRB1, HLA-DQB1 alleles genotypes and its haplotype with infections of HPV,HPV16 in the arcinogenesis of Uighur Women with cervical cancer from the Xinjiang. Analysis he cause and mechanism of HPV infection,cervical cancer of xinjiang uygur in Genetic susceptibility, provide theoretical basis for screening for susceptible population in the future.Method:1) we using gene chip(HybriMax) method to investigate the distribution of HPV and HPV subtype of 370 cervical cancer and 370 normal cervical samples matching by the same area and 117 Cervical cancer lesion,to detect 21 subtypes of HPV, include 13 HPV high-risk types, 5 HPV low-risk types and 3common types 2)using by sequenee-based typing method(PCR-SBT) to investigate HLA-DRB1 Alleles Polymorphism in the 370 cervical cancer and 370 normal cervical samples matching by the same area and 117 cervical cancer lesion,And compare the allele frequency distribution in the three groups 3)using by polymerase chain reaction sequence –specific oligonucleotide method(PCR-SSO)to investigate HLA-DQB1 Alleles Polymorphism in the 200 cervical cance and 200 ormal cervical samples matching by the same area, and compare the allele frequency distribution in the two groups 4) taken 200 cervical cancer and 200 healthy control of Southern Xinjiang from total HLA-DRB1 detection results of Xinjiang, using HLA-DRB1 allele data and HLA-DQB1 data, compare the allele frequency distribution in the two groups.Results:1.Distribution of HPV and Types:1)In total objects: In the 370 of cervical cancer,the positive frequency of HPV 322, the positive rate of HPV 87.0%(322/370);In the 117 of CIN,the positive frequency of HPV 95, the positive rate ofHPV 81.2%(95/117);frequency of HPV subtypes 481,HPV16 was the most common type in cervical cancer patients with the rate of 74.8%(360/481).The positive rate of HPV16 in cervical cancer72.7%(269/370)。2)In southern Xinjiang objects: In the 200 of cervical cancer,the positive frequency of HPV 179, the positive rate of HPV 89.5%( 179/200);frequency of HPV subtypes 219,HPV16 was the most common type in cervical cancer patients with the rate of 80.4%(176/219),The positive rate of HPV16 in cervical cancer81.0%(162/200)。2.The distribution of HLA-DRB1 in HPV infection、CIN and cervical cancer. 1)The frequency of HLA-DRB1*15 in HPV(+)/HPV16(+) was significantly higher than the HPV(-) group( χ2=11.371, P=0.001, OR=1.670,95%CI=1.237-2.254;χ2=7.778,P=0.005,OR=2.782,95%CI=1.318-5.872). The frequency of HLA-DRB1*15 in control group,CIN and cervical cancer was significantly different(χ2=6.743,P=0.034).The frequency of HLA-DRB1*15 in CIN+ and cervical cancer was significantly higher than that the control group(χ2=6.596, P=0.010,OR=1.483,95%CI=1.096-2.006;χ2=6.539,P=0.011,OR=1.511,95%CI=1.099-2.076).2)The frequency of HLA-DRB1*12 in HPV(+) was significantly lower than that the HPV(-)(χ2=8.137,P=0.004,OR=0.441,95%CI=0.248-0.785). The frequency of HLA-DRB1*12 in CIN+ group was significantly lower than the control group(χ2=4.021,P=0.045,OR=0.572,95%CI=0.330-0.994). 3)In the HPV16+ group, the frequency of HLA-DRB1*13 in cervical cancer, CIN and control group was significantly different(χ2=9.759,P=0.008).The frequency of HLA-DRB1*13 in cervical cancer and CIN+ was significantly lower than the control group((χ2=9.704, P=0.002, OR=0.313,95%CI=0.145-0.673;χ2=9.668,P=0.002,OR=0.320,95%CI=0.151-0.679).3.The distribution of HLA-DQB1 in HPV infection and cervical cancer. 1) The frequency of HLA-DQB1*06 in HPV(+) was significantly higher than that the HPV(-)(χ2=6.578,P=0.010, OR=1.572, 95%CI=1.111-2.223). The frequency of HLA-DQB1*06 in HPV16(+) was significantly higher than that the HPV16(-)(χ2=4.272, P=0.039,OR=2.368,95%CI=1.024-5.479). 2) The frequency of HLA-DQB1*03 in HPV(+) was significantly lower than the HPV(-)(χ2=7.930,P=0.005,OR=0.654,95%CI=0.487-0.880).The frequency of HLA-DQB1*03 in cervical cancer was significantly lower than the control group(χ2=8.519,P=0.004,OR=0.645,95%CI=0.480-0.866)4.The distribution of HLA-DRB1-DQB1 in HPV infection and cervical cancer. 1)The frequency of HLA-DRB1*15 和 HLA-DQB1*06 haplotype in HPV(+) was significantly higher than that the HPV(-)(χ2=9.558,P=0.002,OR=2.088,95%CI=1.299-3.356). The frequency of HLA-DRB1*15 和 HLA-DQB1*06 haplotype in cervical cancer was significantlyhigher than that the control group(χ2=8.402,P=0.004,OR=1.997,95%CI=1.242-3.209).2)The frequency of HLA-DRB1*04 和 HLA-DQB1*03 haplotype in cervical cancer was significantly lower than the control group( χ2=4.228, P=0.040, OR=0.584,95%CI=0.348-0.980).Conclusions: 1)HPV16 was the most common type in Xinjiang and southern Xinjiang uyghur cervical cancer. 2.HLA-DRB1: 1) The HLA-DRB1*15 the susceptive gene of Uygur women to HPV/HPV16 infection. Also the susceptive gene to developed from control,CIN, into cervical cancer. The HLA-DRB1*15 the susceptive gene of Uygur women to CIN+ and cervical cancer.2)The HLA-DRB1*12 the protective gene of Uygur women to HPV infection and CIN+.3)In HPV16 positive group, HLA-DRB1*13 also the protective gene to developed from control,CIN, into cervical cancer. HLA-DRB1*13 the protective gene of Uygur women to CIN+ and cervical cancer. 3.HLA-DQB1:1) The HLA-DQB1*06 the susceptive gene of Uygur women to HPV/HPV16 infection. 2) The HLA-DQB1*03 the protective gene of Uygur women to HPV infection and cervical cancer. 4.HLA—DRB1-DQB1 haplotype : 1)TheHLA-DRB1*15 和 HLA-DQB1*06haplotype the susceptive gene of Uyghur women to HPV infection and cervical cancer. 2)The HLA-DRB1*04 和 HLA-DQB1*03 haplotype the protective gene of Uygur women to cervical cancer.