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Common germline variation at the TERT locus contributes to familial clustering of myeloproliferative neoplasms
Author(s) -
Jäger Roland,
Harutyunyan Ashot S.,
Rumi Elisa,
Pietra Daniela,
Berg Tiina,
Olcaydu Damla,
Houlston Richard S.,
Cazzola Mario,
Kralovics Robert
Publication year - 2014
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23842
Subject(s) - single nucleotide polymorphism , genetics , minor allele frequency , haplotype , population , biology , medicine , allele frequency , allele , genotype , gene , environmental health
The C allele of the rs2736100 single nucleotide polymorphism located in the second intron of the TERT gene has recently been identified as a susceptibility factor for myeloproliferative neoplasms (MPN) in the Icelandic population. Here, we evaluate the role of TERT rs2736100_C in sporadic and familial MPN in the context of the previously identified JAK2 GGCC predisposition haplotype. We have confirmed the TERT rs2736100_C association in a large cohort of Italian sporadic MPN patients. The risk conferred by TERT rs2736100_C is present in all molecular and diagnostic MPN subtypes. TERT rs2736100_C and JAK2 GGCC are independently predisposing to MPN and have an additive effect on disease risk, together explaining a large fraction of the population attributable fraction (PAF = 73.06%). We found TERT rs2736100_C significantly enriched ( P = 0.0090) in familial MPN compared to sporadic MPN, suggesting that low‐penetrance variants may be responsible for a substantial part of familial clustering in MPN. Am. J. Hematol. 89:1107–1110, 2014. © 2014 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.