title: TERT rs2736100 genotypes are associated with differential risk of myeloproliferative neoplasms in Swedish and Chinese male patient populations.
abstract: The telomerase reverse transcriptase (TERT) gene rs2736100_C allele has recently been shown to be associated with an increased risk for myeloproliferative neoplasms (MPNs) among Caucasians. However, it is unknown if this association is present in other ethnical populations and whether rs2736100 allele frequencies mirror the incidence of MPNs in a population. Here we genotyped TERT rs2736100 variants in 126 Swedish and 101 Chinese MPN patients and their age-, sex-, and ethnically-matched healthy controls. Healthy Chinese adults had a higher frequency of the A allele and lower frequencies of the C allele compared to Swedish counterparts (57.4 vs 47.0 % for A, 42.6 vs 53.0 % for C, P = 0.006). Both Swedish and Chinese patients harbored significantly higher C allele frequency than their controls (62.7 vs 53.0 % and 57.4 vs 42.6 % for Swedish and Chinese, respectively, P = 0.004). Swedes and Chinese bearing the CC genotype had a significantly increased risk of MPN compared to AA carriers (OR = 2.47; 95 % CI: 1.33-4.57, P = 0.003, for Swedes, and OR = 3.45; 95 % CI: 1.52-7.85, P = 0.005, for Chinese). Further analyses showed that rs2736100_CC was associated with robustly enhanced risk in males only (CC vs AA, OR = 5.11; 95 % CI: 2.19-11.92, P < 0.0001). The CC-carrying MPN patients exhibited significantly higher TERT expression than patients with the AC genotype. Collectively, the rs2736100_C is a risk allele for MPNs in Swedish and Chinese males, and the lower incidence of MPNs in the Chinese population is correlated with a lower rs2736100_C risk allele frequency.
authors: Department of Medicine, Division of Hematology and Center for Molecular Medicine (CMM), Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, 17177, Sweden. Jenny.Dahlstrom@ki.se.
authors: Jenny
authors: J
authors: Dahlström
authors: Department of Pathology, Shandong University School of Medicine, Jinan, China. liu.tiantian@sdu.edu.cn.
authors: Tiantian
authors: T
authors: Liu
authors: Department of Medicine, Division of Hematology and Center for Molecular Medicine (CMM), Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, 17177, Sweden.
authors: Xiaotian
authors: X
authors: Yuan
authors: Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
authors: Leonie
authors: L
authors: Saft
authors: Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
authors: Mehran
authors: M
authors: Ghaderi
authors: Department of Molecular Medicine and Surgery, Neurogenetics Unit, Karolinska Institutet, Stockholm, Sweden.
authors: Ya Bin
authors: YB
authors: Wei
authors: Department of Molecular Medicine and Surgery, Neurogenetics Unit, Karolinska Institutet, Stockholm, Sweden.
authors: Catharina
authors: C
authors: Lavebratt
authors: Shandong University School of Nursing, Jinan, China.
authors: Ping
authors: P
authors: Li
authors: Department of Hematology, The Second Hospital of Shandong University, Jinan, China.
authors: Chengyun
authors: C
authors: Zheng
authors: Department of Medicine, Division of Hematology and Center for Molecular Medicine (CMM), Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, 17177, Sweden.
authors: Magnus
authors: M
authors: Björkholm
authors: Department of Medicine, Division of Hematology and Center for Molecular Medicine (CMM), Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, 17177, Sweden.
authors: Dawei
authors: D
authors: Xu
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D013548:Sweden; D019098:Telomerase / Q000235:genetics*; D059505:Telomere Homeostasis; D044465:White People / Q000235:genetics*
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: Cancer genetics; Myeloproliferative neoplasms; Single nucleotide polymorphism; TERT; Telomerase