+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants

, : Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. New England Journal of Medicine 360(24): 2544-2555

Primary biliary cirrhosis is a chronic granulomatous cholangitis, characteristically associated with antimitochondrial antibodies. Twin and family aggregation data suggest that there is a significant genetic predisposition to primary biliary cirrhosis, but the susceptibility loci are unknown. To identify genetic loci conferring a risk for primary biliary cirrhosis, we carried out a genomewide association analysis in which DNA samples from 2072 Canadian and U.S. subjects (536 patients with primary biliary cirrhosis and 1536 controls) were genotyped for more than 300,000 single-nucleotide polymorphisms (SNPs). Sixteen of the SNPs most strongly associated with primary biliary cirrhosis were genotyped in two independent replication sets. We carried out fine-mapping studies across three loci associated with primary biliary cirrhosis. We found significant associations between primary biliary cirrhosis and 13 loci across the HLA class II region; the HLA-DQB1 locus (encoding the major histocompatibility complex class II, DQ beta chain 1) had the strongest association (P=1.78x10(-19); odds ratio for patients vs. controls, 1.75). Primary biliary cirrhosis was also significantly and reproducibly associated with two SNPs at the IL12A locus (encoding interleukin-12alpha), rs6441286 (P=2.42x10(-14); odds ratio, 1.54) and rs574808 (P=1.88x10(-13); odds ratio, 1.54), and one SNP at the IL12RB2 locus (encoding interleukin-12 receptor beta2), rs3790567 (P=2.76x10(-11); odds ratio, 1.51). Fine-mapping analysis showed that a five-allele haplotype in the 3' flank of IL12A was significantly associated with primary biliary cirrhosis (P=1.15x10(-34)). We found a modest genomewide association (P<5.0x10(-5)) with the risk of disease for SNPs at the STAT4 locus (encoding signal transducer and activator of transcription 4) and the CTLA4 locus (encoding cytotoxic T-lymphocyte-associated protein 4) and 10 other loci. Our data show significant associations between primary biliary cirrhosis and common genetic variants at the HLA class II, IL12A, and IL12RB2 loci and suggest that the interleukin-12 immunoregulatory signaling axis is relevant to the pathophysiology of primary biliary cirrhosis. ( number, NCT00242125.)


PMID: 19458352

DOI: 10.1056/NEJMoa0810440

Other references

M.D.F.lippo; T.R.spandini;, 1998: Geophysical contribution to the study of Bracciano Lake. A Uniboom survey was carried out in Bracciano Lake (Northern Latium) in order to obtain further information about its structural and morphological features. The authors give an updated geophysical interpretation of the lake by combining the findin...

Yau, K.K.W.; Cheung, M-Tong., 2004: Validity of surgical trainee assessment method. Anz Journal of Surgery 74(7): 603-604

Vantassel, Stephen., 2006: The Bailey beaver trap: modifications and sets to improve capture rate. Proceedings of the Vertebrate Pest Conference. December; 22: 171-173

Cantini, E.; Wang, X.; Koelsch, P.; Preece, J.A.; Ma, J.; Mendes, P.M., 2016: Electrically Responsive Surfaces: Experimental and Theoretical Investigations. Stimuli-responsive surfaces have sparked considerable interest in recent years, especially in view of their biomimetic nature and widespread biomedical applications. Significant efforts are continuously being directed at developing functional surf...

Fujino, M.A.; Kawai, T.; Morozumi, A.; Yamamoto, Y.; Ikeda, M.; Suzuki, H., 1992: Endoscopic image manipulation: state of the art. Fundamental techniques and commonly employed algorithms for image manipulation of endoscopic images were reviewed, but only in a few instances was any novel information obtained. New software was recently developed for medium-frequency band enhanc...

Carlberg, Tomas., 2002: Species project in Linnaeus footsteps - Swedish biodiversity Artprojekt i Linnes fotspar - den svenska mangfalden. Fauna och Flora (Uppsala): 971: 2-4

Nyangito, H.O.; Richardson, J.W.; Mundy, D.S.; Mukhebi, A.W.; Zimmel, P.; Namken, J., 1995: Economic impacts of East Coast Fever immunization on smallholder farms, Kenya: a simulation analysis. A whole farm simulation model, Technology Impact Evaluation System (TIES), was used to assess ex-ante financial and economic impacts of immunization of dairy cattle against East Coast Fever (ECF) by the infection and treatment method (ITM) on smal...

Burbank Wilbur Swett, 1932: Grand Junction to Mesa Verde. Report of the

Anonymous, 2016: Call to boost peers with nursing background to House of Lords. Increasing the number of nurse peers in the House of Lords would give the profession more political cache, according to a University of Sydney professor of nursing and midwifery.

Barrot-de la Puente, J.; Mata-Cases, M.; Franch-Nadal, J.; Mundet-Tudurí, X.; Casellas, A.; Fernandez-Real, J.M.; Mauricio, D., 2015: Older type 2 diabetic patients are more likely to achieve glycaemic and cardiovascular risk factors targets than younger patients: analysis of a primary care database. Older subjects with type 2 diabetes mellitus (T2DM) have differential characteristics compared with middle-aged or younger populations, and require tailored management of the disease. To evaluate how clinical characteristics, degree of control of...