Common variants in TMPRSS6 are associated with iron status and erythrocyte volume

被引：200

作者：

Benyamin, Beben ^{[1
]}

Ferreira, Manuel A. R. ^{[1
]}

Willemsen, Gonneke ^{[2
]}

Gordon, Scott ^{[1
]}

Middelberg, Rita P. S. ^{[1
]}

McEvoy, Brian P. ^{[1
]}

Hottenga, Jouke-Jan ^{[2
]}

Henders, Anjali K. ^{[1
]}

Campbell, Megan J. ^{[1
]}

Wallace, Leanne ^{[1
]}

Frazer, Ian H. ^{[3
]}

Heath, Andrew C. ^{[4
,5
]}

de Geus, Eco J. C. ^{[2
]}

Nyholt, Dale R. ^{[1
]}

Visscher, Peter M. ^{[1
]}

Penninx, Brenda W. ^{[6
]}

Boomsma, Dorret I. ^{[2
]}

Martin, Nicholas G. ^{[1
]}

Montgomery, Grant W. ^{[1
]}

Whitfield, John B. ^{[1
]}

机构：

[1] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[2] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

[3] Univ Queensland, Princess Alexandra Hosp, Ctr Immunol & Canc Res, Brisbane, Qld, Australia

[4] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[5] Midwest Alcoholism Res Ctr, St Louis, MO USA

[6] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands

来源：

NATURE GENETICS | 2009年 / 41卷 / 11期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会; 美国国家卫生研究院; 澳大利亚研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; MATRIPTASE-2; TMPRSS6; HEPCIDIN EXPRESSION; SERINE-PROTEASE; DISORDER; HFE;

D O I：

10.1038/ng.456

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 10(-20)), transferrin saturation (combined P = 2.2 x 10(-23)) and erythrocyte mean cell volume (MCV, combined P = 1.1 x 10(-10)). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 x 10(-7)). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.

引用

页码：1173 / 1175

页数：3

共 12 条

[1] Variants in TF and HFE Explain ∼40% of Genetic Variation in Serum-Transferrin Levels [J].

Benyamin, Beben ;

McRae, Allan E. ;

Zhu, Gu ;

Gordon, Scott ;

Henders, Anjali K. ;

Palotie, Aarno ;

Peltonen, Leena ;

Martin, Nicholas G. ;

Montgomery, Grant W. ;

Whitfield, John B. ;

Visscher, Peter M. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 84 (01) :60-65

[2] Genome-wide association of major depression: description of samples for the GAIN Major Depressive Disorder Study: NTR and NESDA biobank projects [J].

Boomsma, Dorret I. ;

Willemsen, Gonneke ;

Sullivan, Patrick F. ;

Heutink, Peter ;

Meijer, Piet ;

Sondervan, David ;

Kluft, Cornelis ;

Smit, Guus ;

Nolen, Willem A. ;

Zitman, Frans G. ;

Smit, Johannes H. ;

Hoogendijk, Witte J. ;

van Dyck, Richard ;

De Geus, Eco J. C. ;

Penninx, Brenda W. J. H. .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2008, 16 (03) :335-342

[3] Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder [J].

Ferreira, Manuel A. R. ;

O'Donovan, Michael C. ;

Meng, Yan A. ;

Jones, Ian R. ;

Ruderfer, Douglas M. ;

Jones, Lisa ;

Fan, Jinbo ;

Kirov, George ;

Perlis, Roy H. ;

Green, Elaine K. ;

Smoller, Jordan W. ;

Grozeva, Detelina ;

Stone, Jennifer ;

Nikolov, Ivan ;

Chambert, Kimberly ;

Hamshere, Marian L. ;

Nimgaonkar, Vishwajit L. ;

Moskvina, Valentina ;

Thase, Michael E. ;

Caesar, Sian ;

Sachs, Gary S. ;

Franklin, Jennifer ;

Gordon-Smith, Katherine ;

Ardlie, Kristin G. ;

Gabriel, Stacey B. ;

Fraser, Christine ;

Blumenstiel, Brendan ;

Defelice, Matthew ;

Breen, Gerome ;

Gill, Michael ;

Morris, Derek W. ;

Elkin, Amanda ;

Muir, Walter J. ;

McGhee, Kevin A. ;

Williamson, Richard ;

MacIntyre, Donald J. ;

MacLean, Alan W. ;

Clair, David St ;

Robinson, Michelle ;

Van Beck, Margaret ;

Pereira, Ana C. P. ;

Kandaswamy, Radhika ;

McQuillin, Andrew ;

Collier, David A. ;

Bass, Nicholas J. ;

Young, Allan H. ;

Lawrence, Jacob ;

Ferrier, I. Nicol ;

Anjorin, Adebayo ;

Farmer, Anne .

NATURE GENETICS, 2008, 40 (09) :1056-1058

[4] Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA) [J].

Finberg, Karin E. ;

Heeney, Matthew M. ;

Campagna, Dean R. ;

Aydinok, Yesim ;

Pearson, Howard A. ;

Hartman, Kip R. ;

Mayo, Mary M. ;

Samuel, Stewart M. ;

Strouse, John J. ;

Markianos, Kyriacos ;

Andrews, Nancy C. ;

Fleming, Mark D. .

NATURE GENETICS, 2008, 40 (05) :569-571

[5] Interaction of the Hereditary Hemochromatosis Protein HFE with Transferrin Receptor 2 Is Required for Transferrin-Induced Hepcidin Expression [J].

Gao, Junwei ;

Chen, Juxing ;

Kramer, Maxwell ;

Tsukamoto, Hidekazu ;

Zhang, An-Sheng ;

Enns, Caroline A. .

CELL METABOLISM, 2009, 9 (03) :217-227

[6] A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron [J].

Melis, Maria Antonietta ;

Cau, Milena ;

Congiu, Rita ;

Sole, Gabriella ;

Barella, Susanna ;

Cao, Antonio ;

Westerman, Mark ;

Cazzola, Mario ;

Galanello, Renzo .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2008, 93 (10) :1473-1479

[7] Fine tuning of hepcidin expression by positive and negative regulators [J].

Muckenthaler, Martina U. .

CELL METABOLISM, 2008, 8 (01) :1-3

[8] PLINK: A tool set for whole-genome association and population-based linkage analyses [J].

Purcell, Shaun ;

Neale, Benjamin ;

Todd-Brown, Kathe ;

Thomas, Lori ;

Ferreira, Manuel A. R. ;

Bender, David ;

Maller, Julian ;

Sklar, Pamela ;

de Bakker, Paul I. W. ;

Daly, Mark J. ;

Sham, Pak C. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (03) :559-575

[9] Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis [J].

Ramsay, Andrew J. ;

Hooper, John D. ;

Folgueras, Alicia R. ;

Velasco, Gloria ;

Lopez-Otin, Carlos .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2009, 94 (06) :840-849

[10] Mapping the genetic architecture of gene expression in human liver [J].

Schadt, Eric E. ;

Molony, Cliona ;

Chudin, Eugene ;

Hao, Ke ;

Yang, Xia ;

Lum, Pek Y. ;

Kasarskis, Andrew ;

Zhang, Bin ;

Wang, Susanna ;

Suver, Christine ;

Zhu, Jun ;

Millstein, Joshua ;

Sieberts, Solveig ;

Lamb, John ;

GuhaThakurta, Debraj ;

Derry, Jonathan ;

Storey, John D. ;

Avila-Campillo, Iliana ;

Kruger, Mark J. ;

Johnson, Jason M. ;

Rohl, Carol A. ;

van Nas, Atila ;

Mehrabian, Margarete ;

Drake, Thomas A. ;

Lusis, Aldons J. ;

Smith, Ryan C. ;

Guengerich, F. Peter ;

Strom, Stephen C. ;

Schuetz, Erin ;

Rushmore, Thomas H. ;

Ulrich, Roger .

PLOS BIOLOGY, 2008, 6 (05) :1020-1032

← 1 2 →