title: Single nucleotide polymorphism (SNP) analysis demonstrates a significant association of tumour necrosis factor-alpha (TNFA) with primary immune thrombocytopenia among Caucasian adults.
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.
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. avs31@medschl.cam.ac.uk
authors.forename: Ameet
authors.initials: A
authors.lastname: Sarpatwari
authors.forename: James B
authors.initials: JB
authors.lastname: Bussel
authors.forename: Momin
authors.initials: M
authors.lastname: Ahmed
authors.forename: Sebhat
authors.initials: S
authors.lastname: Erqou
authors.forename: John W
authors.initials: JW
authors.lastname: Semple
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Newland
authors.forename: Dimitri
authors.initials: D
authors.lastname: Bennett
authors.forename: Paul
authors.initials: P
authors.lastname: Pharoah
authors.forename: Drew
authors.initials: D
authors.lastname: Provan
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology; D013921:Thrombocytopenia / Q000097:blood / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D016207:Cytokines; D018121:Receptors, Cytokine; D014409:Tumor Necrosis Factor-alpha