62 Abstracts C-5.2 #111 TAPI AND TAP2 POLYMORPHISMS IN MULTIPLE SCLEROSIS PATIEntS. D Middleton, G Megaw, D Savage. N. Ireland Tissue Typing Laboratory, City Hospital, Belfast, N. Ireland. Previous reports have shown the association of HLA-DR2 with multiple sclerosis (MS) - in particular the involvement of the HLA- DRIS-DQ6 haplotype. We and others have reported that this association does not extend to the HIA-DP locus. Two genes TAPI and TAP2 map in the major histocompatibility class II region between HLA-DQ and HIA-DP. The products of these two genes are involved in the active transport of antigenic peptides across the endoplasmic reticulum. In this study polymorphisms in TAPI at codon positions 333 (VAL or ILE), 637 (ASP or GLY) and TAP2 at codon positions 379 (VAL or ILE), 565 (ALA or THR), 665 (ALA or THR) were identified using the amplification refractory mutation system (.ARMS) polymerase chain reaction (PCR) method in 48 MS patients and 150 controls. We found significant reductions in the following polymomphisms in MS patients, rAP2 ILE-379 (37% in controls; 15% in patients P<.O02), TAP2 THR-565 (31% in controls; 10% in patients P<.O04). When the patients and controls were grouped into DRl5+ve and DRl5-ve both of these reductions were found to be significant in only the DRlS-ve patients (ILE-379 39% in controls; 6% in patients, P<.O03, THR-565 37% in controls; 6% in patients P<.O05). However when we selected 48 controls, each HIA-DR matched to one of the patients, we no longer found differences in the frequencies of either of the polymorphisms. It would appear that t~ae increase in these polymorphisms is due to their positive linkage with HLA-DR4 and their negative linkage to IiLA-DR3. HI~A-DR3 is increased and HLA-OR4 decreased in the MS patients relative to tile controls. C-5.2 #112 HLA DR-DQ DISEASE ASSOCIATIONS IN HISPANIC CERVICAL CARCINOMA. R Apple ~, C Wheeler:, T Becker:, W Klitz 3, and H Erlich~,~Departrnent of Human Genetics, Roche Molecular Systems, Alameda, CA; 2UNM Cancer Center, New Mexico Tumor Registry, Albuquerque, NM; 3Department of Integrative Biology, University of California, Berkeley, CA. Human papillomaviruses (HPV) have been demonstrated to be a contributing factor in the development of cervical intraepithelial neoplasia and carcinoma. In addition, HLA associations with cervical carcinoma (CC) and the serologic DQw3 specificity have been reported. In this study, HPV and HLA class II DR and DQ PCR/sequence specific oligonucleotide probe (SSOP) typing was perfonned on paraffin embedded biopsies from 98 Hispanic CC patients and cervical scrapings from 220 regionally and ethnically matched controls with nonnal pap smears and no past history of cervical disease. HPV was detected by amplification of the L1 capsid and E6 transforming genes, and typed using a series of HPV SSOPs. HPV was detected in 79/89 amplifiable tumor biopsies; 53 of these were positive for HPVI6. Frequencies of all DQBI alleles, including the DQBI alleles encoding the DQw3 specificity (DQBI*0301, *0302, and *0303), were similar among patients and controls. However patient and control DR-DQ haplotype frequencies differed significantly (p<0.005), and specific haplotypes were associated with CC susceptibility and resistance. Furthermore, these DR-DQ associations were HPV type-specific. The strongest DRB 1- DQBI association was seen with DRBI*I501-DQBI*0602 (RR=5.1), which was specific for HPV16 cancers. A HPV16 specific association was also noted with DRBI*0407-DQBI*0302. In addition, several DRI3 haplotypes were negatively associated, or protective with HPVI6 ÷ CC, whereas DR14 was protective with non- HPV 16 cervical cancers.

HLA DR-DQ disease associations in hispanic cervical carcinoma

Download PDF Report

Upload
truongkiet
View
213
Download
1

Embed Size (px)

Citation preview

Page 1: HLA DR-DQ disease associations in hispanic cervical carcinoma

62 Abstracts

C-5.2 #111

TAPI AND TAP2 POLYMORPHISMS IN MULTIPLE SCLEROSIS PATIEntS. D Middleton, G Megaw, D Savage. N. Ireland Tissue Typing Laboratory, City Hospital, Belfast, N. Ireland.

Previous reports have shown the association of HLA-DR2 with multiple sclerosis (MS) - in particular the involvement of the HLA- DRIS-DQ6 haplotype. We and others have reported that this association does not extend to the HIA-DP locus. Two genes TAPI and TAP2 map in the major histocompatibility class II region between HLA-DQ and HIA-DP. The products of these two genes are involved in the active transport of antigenic peptides across the endoplasmic reticulum. In this study polymorphisms in TAPI at codon positions 333 (VAL or ILE), 637 (ASP or GLY) and TAP2 at codon positions 379 (VAL or ILE), 565 (ALA or THR), 665 (ALA or THR) were identified using the amplification refractory mutation system (.ARMS) polymerase chain reaction (PCR) method in 48 MS patients and 150 controls.

We found significant reductions in the following polymomphisms in MS patients, rAP2 ILE-379 (37% in controls; 15% in patients P<.O02), TAP2 THR-565 (31% in controls; 10% in patients P<.O04). When the patients and controls were grouped into DRl5+ve and DRl5-ve both of these reductions were found to be significant in only the DRlS-ve patients (ILE-379 39% in controls; 6% in patients, P<.O03, THR-565 37% in controls; 6% in patients P<.O05). However when we selected 48 controls, each HIA-DR matched to one of the patients, we no longer found differences in the frequencies of either of the polymorphisms. It would appear that t~ae increase in these polymorphisms is due to their positive linkage with HLA-DR4 and their negative linkage to IiLA-DR3. HI~A-DR3 is increased and HLA-OR4 decreased in the MS patients relative to tile controls.

C-5.2 #112

HLA DR-DQ DISEASE ASSOCIATIONS IN HISPANIC CERVICAL CARCINOMA. R Apple ~, C Wheeler:, T Becker:, W Klitz 3, and H Erlich~,~Departrnent of Human Genetics, Roche Molecular Systems, Alameda, CA; 2UNM Cancer Center, New Mexico Tumor Registry, Albuquerque, NM; 3Department of Integrative Biology, University of California, Berkeley, CA.

Human papillomaviruses (HPV) have been demonstrated to be a contributing factor in the development of cervical intraepithelial neoplasia and carcinoma. In addition, HLA associations with cervical carcinoma (CC) and the serologic DQw3 specificity have been reported. In this study, HPV and HLA class II DR and DQ PCR/sequence specific oligonucleotide probe (SSOP) typing was perfonned on paraffin embedded biopsies from 98 Hispanic CC patients and cervical scrapings from 220 regionally and ethnically matched controls with nonnal pap smears and no past history of cervical disease. HPV was detected by amplification of the L1 capsid and E6 transforming genes, and typed using a series of HPV SSOPs. HPV was detected in 79/89 amplifiable tumor biopsies; 53 of these were positive for HPVI6. Frequencies of all DQBI alleles, including the DQBI alleles encoding the DQw3 specificity (DQBI*0301, *0302, and *0303), were similar among patients and controls. However patient and control DR-DQ haplotype frequencies differed significantly (p<0.005), and specific haplotypes were associated with CC susceptibility and resistance. Furthermore, these DR-DQ associations were HPV type-specific. The strongest DRB 1- DQBI association was seen with DRBI*I501-DQBI*0602 (RR=5.1), which was specific for HPV16 cancers. A HPV16 specific association was also noted with DRBI*0407-DQBI*0302. In addition, several DRI3 haplotypes were negatively associated, or protective with HPVI6 ÷ CC, whereas DR14 was protective with non- HPV 16 cervical cancers.