RESUMO
We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.
Assuntos
Autoimunidade/genética , Neoplasias da Mama/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único/genética , Espondilite Anquilosante/genética , Tireoidite Autoimune/genética , Aminopeptidases/genética , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Mapeamento Cromossômico , Genética Populacional , Genótipo , Haplótipos/genética , Humanos , Desequilíbrio de Ligação , Antígenos de Histocompatibilidade Menor , Esclerose Múltipla/epidemiologia , América do Norte/epidemiologia , Reação em Cadeia da Polimerase , Receptores Imunológicos/genética , Receptores de Interleucina/genética , Espondilite Anquilosante/epidemiologia , Tireoidite Autoimune/epidemiologiaRESUMO
BACKGROUND: NAT was introduced for HCV RNA in 1999 to screen blood donations and improve the safety of the blood supply. STUDY DESIGN AND METHODS: The performance of a NAT multiplex for HCV and HIV-1 RNA based on transcription-mediated amplification (TMA) was assessed with various sensitivity panels and by screening 50,000 serologically unscreened, first-time donor plasma samples. Results were compared with a routine NAT screening for HCV RNA by RT-PCR in pools of 96 plasma samples. RESULTS: The TMA multiplex 95 percent sensitivity ranged between 22 and 54 IU per mL for HIV-1 and 15 and 20 IU per mL for HCV RNA. The rate of test failure was 8.6 percent but decreased to 4.7 percent when results of two critical periods of equipment malfunction were excluded. Test failure was related to human error, minute control contamination, and insufficient mixing of reagents at the extraction stage. All 31 repeatedly reactive samples (0.06%) were seropositive for HCV (29) or HIV-1 (2) and contained RNA detectable by discriminatory TMA and confirmatory RT-PCR, indicating 100 percent specificity. A direct comparison of TMA in individual samples and RT-PCR in plasma pools was possible on 27 HCV RNA-containing samples. Twenty-six samples were detected in plasma pools; the lack of detection of 1 sample was due to an identification error at the pooling stage. CONCLUSION: The HCV and HIV-1 multiplex NAT had high specificity and sensitivity.