Abstract:
:One of the most severe and important complication in the treatment of haemophilia A (HA) patients is the formation of inhibitors. The mechanism that leads to factor (F)VIII inhibitor formation is complicated. Both genetic and environmental factors have been mentioned to play decisive roles. Recently, polymorphisms in the genes encoding interleukin-10 (IL-10), tumour necrosis factor-alpha (TNF-α), cytotoxic T-lymphocyte antigen-4 (CTLA-4), have been suggested to be contributing determinants of the inhibitor risk. In order to investigate the influence of the single nucleotide polymorphisms (SNPs) in the genes encoding for cytokines to the inhibitors development in Chinese HA patients, we genotyped 10 SNPs with high heterozygote rates in Chinese and a CA repeat microsatellite at the gene loci IL-10 as well in a separate, unrelated case-controlled cohort of 122 affected HA patients; 63 with inhibitors and 59 without inhibitors. The particular SNPs included in this study were as follows: -592C/A and -819C/T in IL-10, -590C/T in IL-4, -318C/T and 49A/G in CTLA-4, -827C/T in TNF-α, -1112C/T and 2044G/A in IL-13, 874A/T in interferon (IFN)-γ and -295T/C in IL-16. Our results demonstrated that -819T and -592A alleles in IL-10 were observed more frequently in patients with inhibitors. This indicated that -819C/T and -592A/C in IL-10 may influence the inhibitors development in HA patients. Furthermore, we concluded that the haplotype in IL-10 (TA, CA, CC at positions -819 and -582, respectively) may predispose FVIII inhibitor development in HA patients. In conclusion, the data reported in our study clearly highlight the participation of IL-10 in inhibitors formation in Chinese HA patients.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Lu Y,Ding Q,Dai J,Wang H,Wang Xdoi
10.1160/TH11-06-0425subject
Has Abstractpub_date
2012-01-01 00:00:00pages
30-6issue
1eissn
0340-6245issn
2567-689Xpii
11-06-0425journal_volume
107pub_type
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