Susceptibility loci for preeclampsia on chromosomes 2p25 and 9p13 in Finnish families
Susceptibility loci for preeclampsia on chromosomes 2p25 and 9p13 in Finnish families
复制标题
DOI：
10.1086/345311
复制
发表时间：
2003-01-01
影响因子：
9.8
通讯作者：
Kere, J
中科院分区：
文献类型：
--
作者：
Laivuori, H;Lahermo, P;Kere, J
先兆子痫是一种常见的妊娠特有疾病，其特征是胎盘血流减少、内皮功能障碍、血压升高和蛋白尿。这种异质性疾病的发病机制尚不完全清楚，但它具有家族性成分，这表明一个或多个常见的等位基因可能是易感基因。我们假设，在创始人群体中，先兆子痫的遗传背景也可能显示出减少的异质性，我们对主要在芬兰中东部凯努乌省招募的15个多胎家庭进行了全基因组扫描。我们发现了两个超过显著连锁阈值的基因座：2p25，靠近标记D2S168(非参数连锁得分3.77；P=.000761)，位于21.70 cM；9p13，靠近标记D9S169(非参数连锁得分3.74；)，位于38.90 cM。在163.00 cM处，D4S413与D4S3046之间存在一个位于染色体4q32上的连锁位点(NPL值3.13；P=0.003238)。在本研究中，染色体2p25上的易感基因座(21.7 cM)与冰岛研究中发现的2p12上的易感基因座(94.05 cM)和澳大利亚/新西兰研究中发现的2q23上的易感基因座(144.7 cM)明显不同。在芬兰和中国最近发表的两项全基因组扫描中，9p13的基因座被证明是2型糖尿病的候选区域。染色体2p25和9p13区域可能含有子痫前期的易感基因。
Preeclampsia is a common, pregnancy-specific disorder characterized by reduced placental perfusion, endothelial dysfunction, elevated blood pressure, and proteinuria. The pathogenesis of this heterogeneous disorder is incompletely understood, but it has a familial component, which suggests that one or more common alleles may act as susceptibility genes. We hypothesized that, in a founder population, the genetic background of preeclampsia might also show reduced heterogeneity, and we have performed a genomewide scan in 15 multiplex families recruited predominantly in the Kainuu province in central eastern Finland. We found two loci that exceeded the threshold for significant linkage: chromosome 2p25, near marker D2S168 (nonparametric linkage [NPL] score 3.77; P = .000761) at 21.70 cM, and 9p13, near marker D9S169 (NPL score 3.74;) at P = .000821) at 38.90 cM. In addition, there was a locus showing suggestive linkage at chromosome 4q32 between D4S413 and D4S3046 (NPL score 3.13; P = .003238) at 163.00 cM. In the present study the susceptibility locus on chromosome 2p25 is clearly different (21.70 cM) from the locus at 2p12 found in an Icelandic study (94.05 cM) and the locus at 2q23 (144.7 cM) found in an Australian/New Zealand study. The locus at 9p13 has been shown to be a candidate region for type 2 diabetes in two recently published genomewide scans from Finland and China. The regions on chromosomes 2p25 and 9p13 may harbor susceptibility genes for preeclampsia.