Pajukanta P, Cargill M, Viitanen L, Nuotio I, Kareinen A, Perola M, Terwilliger J D, Kempas E, Daly M, Lilja H, Rioux J D, Brettin T, Viikari J S, Rönnemaa T, Laakso M, Lander E S, Peltonen L
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Am J Hum Genet. 2000 Dec;67(6):1481-93. doi: 10.1086/316902. Epub 2000 Nov 13.
Coronary heart disease (CHD) is a complex disorder constituting a major health problem in Western societies. To assess the genetic background of CHD, we performed a genomewide linkage scan in two study samples from the genetically isolated population of Finland. An initial study sample consisted of family material from the northeastern part of Finland, settled by a small number of founders approximately 300 years ago. A second study sample originated from the southwestern region of Finland, settled approximately 2,000 years ago. Families were ascertained through probands exhibiting premature CHD, defined as >50% stenosis of at least two coronary arteries at a young age, as verified by coronary angiography. Both study samples and the pooled data set provided evidence for linkage in two chromosomal regions. A region on chromosome 2q21.1-22 yielded two-point LOD scores of 3.2, 1.9, and 3.7, in the affected sib-pair (ASP) analyses of the northeastern, southwestern, and pooled study samples. The corresponding multipoint maximum-likelihood scores (MLSs) for these three study samples were 2.4, 1.3, and 3.0. In addition, a region on chromosome Xq23-26 resulted in two-point LOD scores of 1.9, 3.5, and 2.9 and in multipoint MLSs of 3.4, 3.1, and 2.5, respectively. In conclusion, this study identifies two loci likely to contribute to premature CHD: one on chromosome 2q21.1-22 and another on chromosome Xq23-26.
冠心病（CHD）是一种复杂的疾病，在西方社会构成了一个主要的健康问题。为了评估冠心病的遗传背景，我们在来自芬兰遗传隔离人群的两个研究样本中进行了全基因组连锁扫描。最初的研究样本由芬兰东北部的家族材料组成，大约在300年前由少数奠基者定居于此。第二个研究样本来自芬兰西南部地区，大约在2000年前定居。通过患有早发性冠心病的先证者确定家族，早发性冠心病定义为经冠状动脉造影证实，在年轻时至少两条冠状动脉狭窄>50%。两个研究样本和合并数据集都提供了两个染色体区域存在连锁的证据。在对东北部、西南部和合并研究样本的受累同胞对（ASP）分析中，2q21.1 - 22染色体区域的两点LOD得分分别为3.2、1.9和3.7。这三个研究样本对应的多点最大似然得分（MLS）分别为2.4、1.3和3.0。此外，Xq23 - 26染色体区域的两点LOD得分分别为1.9、3.5和2.9，多点MLS分别为3.4、3.1和2.5。总之，本研究确定了两个可能导致早发性冠心病的基因座：一个在2q21.1 - 22染色体上，另一个在Xq23 - 26染色体上。
