生物谷报道：美国密执根大学公共卫生学院主持的一项国际研究日前发现了7种影响血液中胆固醇浓度的基因，并确认了之前认为对胆固醇有影响的其他11种基因。有关论文1月13日发表在《自然.遗传学》在线版上。
该研究的主要目标是寻找影响血脂水平的基因突变，并确认这些突变是否与心脏病的发病率有关。研究人员借助人类基因组单体型图计划（HapMap）对8800个个体中的200万个基因变异进行了筛选，并最终将目标锁定在18个基因的25种变异上。研究人员表示，确定影响胆固醇含量的基因突变有助于找到更有效的心脏病治疗方法。此次发现的与低密度脂蛋白胆固醇（LDL）含量有关的基因突变都会影响冠状动脉疾病的发病率，这表明以这些基因为靶向的药物治疗能有效预防冠状动脉疾病。
研究人员同时表示，虽然研究发现有些基因突变会提高人体低密度脂蛋白胆固醇（LDL）的含量并增加患心脏病的几率，但似乎影响高密度脂蛋白胆固醇（HDL）的基因突变并不会降低患冠状动脉疾病的风险。因此，研究结果可能使医学界重新考虑HDL胆固醇和LDL胆固醇对心脏病的影响。
冠状动脉疾病是目前发病率最高的心脏病，也是工业化国家死亡率最高的疾病之一。它可能会引起心脏病发作、中风、心绞痛及其他不良心脏反应。冠状动脉疾病的发病率受到胆固醇的种类和含量以及血液中的油脂的影响，而遗传因素和环境状况都对人体胆固醇和血脂含量有影响。（科技日报）
生物谷推荐英文原文：
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: skathiresan@partners.org
Correspondence to: Marju Orho-Melander6 e-mail: marju.orho-melander@med.lu.se
