4个独立的研究小组在日前在线出版的《自然—遗传学》期刊上报道说，34个新的遗传位点与血细胞性状特征有关。新发现提供了有关遗传位点影响血细胞性状的新认识。
为了帮助多种疾病的诊断和治疗，如癌症、心血管疾病、代谢疾病、传染病和免疫系统疾病，临床中普遍需要测试血细胞的数目和容量。Nicole Soranzo和Santhi Ganesh与同事合作，对近5万名受试者的血液进行了测试。同时，他们的研究还报告了25个与临床血液特征相关的遗传位点，包括血色素的水平，红细胞、 白细胞和血小板的数目与容量等。
Beben Benyamin、John Chambers和Jaspal Kooner与同事合作，分别独立证实了基因TMPRSS6与血小板水平有关，Soranzo和Ganesh也证实了这一相关性。因为以前的研究显 示，TMPRSS6中的缺陷与铁难融性贫血和铁不足性贫血有关，新发现则表明，TMPRSS6参与了普通人体内的铁离子水平控制。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Genetics 41, 1182 - 1190 (2009) 11 October 2009 | doi:10.1038/ng.467
A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium
The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
Nature Genetics 41, 1191 - 1198 (2009) 11 October 2009 | doi:10.1038/ng.466
Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium
Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 10-8 to 7 10-86). Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures.
Nature Genetics 41, 1173 - 1175 (2009) 11 October 2009 | doi:10.1038/ng.456
Common variants in TMPRSS6 are associated with iron status and erythrocyte volume
We report a genome-wide association study to iron status. We identify an association of SNPs in TPMRSS6 to serum iron (rs855791, combined P = 1.5 10-20), transferrin saturation (combined P = 2.2 10-23) and erythrocyte mean cell volume (MCV, combined P = 1.1 10-10). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 10-7). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.
Nature Genetics 41, 1170 - 1172 (2009) 11 October 2009 | doi:10.1038/ng.462
Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels
John C Chambers1,13, Weihua Zhang1,13, Yun Li2, Joban Sehmi3, Mark N Wass4, Delilah Zabaneh1, Clive Hoggart1, Henry Bayele5, Mark I McCarthy6, Leena Peltonen7, Nelson B Freimer8, Surjit K Srai5, Patrick H Maxwell9, Michael J E Sternberg4, Aimo Ruokonen10, Gon?alo Abecasis2, Marjo-Riitta Jarvelin1,11,12, James Scott3,13, Paul Elliott1,13 & Jaspal S Kooner3,13
We carried out a genome-wide association study of hemoglobin levels in 16,001 individuals of European and Indian Asian ancestry. The most closely associated SNP (rs855791) results in nonsynonymous (V736A) change in the serine protease domain of TMPRSS6 and a blood hemoglobin concentration 0.13 (95% CI 0.09–0.17) g/dl lower per copy of allele A (P = 1.6 10-13). Our findings suggest that TMPRSS6, a regulator of hepcidin synthesis and iron handling, is crucial in hemoglobin level maintenance.
