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Abstract
T-helper 1 polarization in patients with primary immune thrombocytopenia (ITP) is well documented. However, the genetic contribution to this imbalance remains unclear. To address this question, we selected six candidate single nucleotide polymorphisms within cytokine or cytokine receptor genes for association testing among Caucasian adults. Patients from the United Kingdom Adult ITP Registry were gender-matched (1∶3) with healthy controls from the Wellcome Trust Case Control Consortium. Variants IL10 −819 c>t, TNFA −308 g>a, TGFB1 −509 c>t, IL1A −889 c>t, IL10 −592 c>t, and IL4R q576r were measured in cases and retrieved for controls from the European Genome-phenome Archive. Associations were evaluated using logistic regression models. In total, 206 patients with primary ITP were matched with 618 controls. A significant per allele odds ratio of 1·34 (95% confidence interval, 1·03–1·75; P = 0·03) was observed for TNFA −308 g>a, implicating an increased disease susceptibility among Caucasian carriers of the rare allele.
The authors thank Dr Charles A Mein for overseeing the genotyping of primary ITP DNA samples, Drs Lynne Condreay and Andres Brainsky for their critical review of the manuscript, and the Wellcome Trust Case−Control Consortium for access to genome-wide data on the 1958 British Birth Cohort. The authors are additionally indebted to our student research assistants: Drs Sarene Saw, Tie Sing Fong, Helen Ngu, Wan Jun Ng, Ei Leen Lim, and Sazlyna Mohd Sazily Lim for their assistance in extracting data from hospital medical records. Lastly, this work would not have been possible without the collaboration of haematologists throughout the United Kingdom. The investigation was supported in part by the UK ITP Support Association, Amgen Europe, and GlaxoSmithKline. This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under awards 076113 and 08475.