生物谷報(bào)道：美國(guó)密執(zhí)根大學(xué)公共衛(wèi)生學(xué)院主持的一項(xiàng)國(guó)際研究日前發(fā)現(xiàn)了7種影響血液中膽固醇濃度的基因,，并確認(rèn)了之前認(rèn)為對(duì)膽固醇有影響的其他11種基因。有關(guān)論文1月13日發(fā)表在《自然.遺傳學(xué)》在線版上,。
該研究的主要目標(biāo)是尋找影響血脂水平的基因突變,，并確認(rèn)這些突變是否與心臟病的發(fā)病率有關(guān)。研究人員借助人類基因組單體型圖計(jì)劃（HapMap）對(duì)8800個(gè)個(gè)體中的200萬個(gè)基因變異進(jìn)行了篩選,，并最終將目標(biāo)鎖定在18個(gè)基因的25種變異上。研究人員表示,，確定影響膽固醇含量的基因突變有助于找到更有效的心臟病治療方法,。此次發(fā)現(xiàn)的與低密度脂蛋白膽固醇（LDL）含量有關(guān)的基因突變都會(huì)影響冠狀動(dòng)脈疾病的發(fā)病率，這表明以這些基因?yàn)榘邢虻乃幬镏委熌苡行ьA(yù)防冠狀動(dòng)脈疾病,。
研究人員同時(shí)表示,，雖然研究發(fā)現(xiàn)有些基因突變會(huì)提高人體低密度脂蛋白膽固醇（LDL）的含量并增加患心臟病的幾率，但似乎影響高密度脂蛋白膽固醇（HDL）的基因突變并不會(huì)降低患冠狀動(dòng)脈疾病的風(fēng)險(xiǎn),。因此,，研究結(jié)果可能使醫(yī)學(xué)界重新考慮HDL膽固醇和LDL膽固醇對(duì)心臟病的影響。
冠狀動(dòng)脈疾病是目前發(fā)病率最高的心臟病,，也是工業(yè)化國(guó)家死亡率最高的疾病之一,。它可能會(huì)引起心臟病發(fā)作、中風(fēng),、心絞痛及其他不良心臟反應(yīng),。冠狀動(dòng)脈疾病的發(fā)病率受到膽固醇的種類和含量以及血液中的油脂的影響，而遺傳因素和環(huán)境狀況都對(duì)人體膽固醇和血脂含量有影響,。（科技日?qǐng)?bào)）
生物谷推薦英文原文：
Nature Genetics
Published online: 13 January 2008 | doi:10.1038/ng.75
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans
Sekar Kathiresan1,2,3, Olle Melander4, Candace Guiducci2, Aarti Surti2, Noël P Burtt2, Mark J Rieder5, Gregory M Cooper5, Charlotta Roos6, Benjamin F Voight2,7,8, Aki S Havulinna9, Björn Wahlstrand10, Thomas Hedner10, Dolores Corella11, E Shyong Tai12, Jose M Ordovas13, Göran Berglund14, Erkki Vartiainen9, Pekka Jousilahti9, Bo Hedblad15, Marja-Riitta Taskinen16, Christopher Newton-Cheh1,2,3, Veikko Salomaa9, Leena Peltonen2,9,17,18, Leif Groop6,19, David M Altshuler2,3,7,8,20 & Marju Orho-Melander6
Blood concentrations of lipoproteins and lipids are heritable1 risk factors for cardiovascular disease2, 3. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue4) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of these loci are new (P < 5 10-8 for each new locus). Of the six newly identified chromosomal regions, two were associated with LDL cholesterol (1p13 near CELSR2, PSRC1 and SORT1 and 19p13 near CILP2 and PBX4), one with HDL cholesterol (1q42 in GALNT2) and five with triglycerides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13 near CILP2 and PBX4 and 1p31 near ANGPTL3). At 1p13, the LDL-associated SNP was also strongly correlated with CELSR2, PSRC1, and SORT1 transcript levels in human liver, and a proxy for this SNP was recently shown to affect risk for coronary artery disease5. Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care.
Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Program in Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Department of Clinical Sciences, Hypertension and Cardiovascular Diseases, University Hospital Malmö, Lund University, Malmö 20502, Sweden.
Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmö, Lund University, Malmö 20502, Sweden.
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
National Public Health Institute Helsinki 00300, Finland.
Department of Clinical Pharmacology, Sahlgrenska University Hospital, Göteborg 41345, Sweden.
Department of Preventive Medicine, School of Medicine, University of Valencia, Valencia 46010, Spain.
Department of Endocrinology, Singapore General Hospital, 169608 Singapore.
Nutrition and Genomics Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA.
Department of Internal Medicine, University Hospital Malmö, Lund University, Malmö 20502, Sweden.
Department of Epidemiological Research, University Hospital Malmö, Lund University, Malmö 20502, Sweden.
Department of Medicine, University of Helsinki, Helsinki 00029, Finland.
Department of Medical Genetics, University of Helsinki, Helsinki 00029, Finland.
Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
Department of Medicine, Helsinki University Hospital, Helsinki 00029, Finland.
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Correspondence to: Sekar Kathiresan1,2,3 e-mail: [email protected]
Correspondence to: Marju Orho-Melander6 e-mail: [email protected]
