4個獨(dú)立的研究小組在日前在線出版的《自然—遺傳學(xué)》期刊上報道說,，34個新的遺傳位點(diǎn)與血細(xì)胞性狀特征有關(guān)。新發(fā)現(xiàn)提供了有關(guān)遺傳位點(diǎn)影響血細(xì)胞性狀的新認(rèn)識,。

為了幫助多種疾病的診斷和治療,，如癌癥、心血管疾病,、代謝疾病,、傳染病和免疫系統(tǒng)疾病，臨床中普遍需要測試血細(xì)胞的數(shù)目和容量,。Nicole Soranzo和Santhi Ganesh與同事合作,，對近5萬名受試者的血液進(jìn)行了測試。同時,，他們的研究還報告了25個與臨床血液特征相關(guān)的遺傳位點(diǎn),，包括血色素的水平，紅細(xì)胞,、 白細(xì)胞和血小板的數(shù)目與容量等,。

Beben Benyamin、John Chambers和Jaspal Kooner與同事合作,，分別獨(dú)立證實(shí)了基因TMPRSS6與血小板水平有關(guān),，Soranzo和Ganesh也證實(shí)了這一相關(guān)性。因?yàn)橐郧暗难芯匡@ 示,，TMPRSS6中的缺陷與鐵難融性貧血和鐵不足性貧血有關(guān),，新發(fā)現(xiàn)則表明,，TMPRSS6參與了普通人體內(nèi)的鐵離子水平控制。（生物谷Bioon.com）

生物谷推薦原始出處：

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.