Association of pre-eclampsia with common coding sequence variations in the lipoprotein lipase gene.
Association of pre-eclampsia with common coding sequence variations in the lipoprotein lipase gene.
复制标题
先兆子痫与脂蛋白脂肪酶基因中常见编码序列变异的关联。
DOI：
10.1034/j.1399-0004.1999.560406.x
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发表时间：
1999
影响因子：
3.5
通讯作者：
Ferrell,RE
中科院分区：
文献类型：
--
作者：
Hubel,CA;Roberts,JM;Ferrell,RE
明显的血脂异常可能导致子痫前期内皮细胞功能障碍。携带脂蛋白脂肪酶（LPL）基因N291S或D9N错义突变的人表现出LPL活性降低，易患血脂异常和心血管疾病。在白种人中，D9N变异与−93T→G启动子变异存在强烈的连锁不平衡。第四种LPL变体S447X通常与有益的脂质谱有关。我们询问与正常妊娠相比，N291S和D9N/ - 93T→G组合变异是否在患有子痫前期的高加索妇女中更普遍，而S447X变异是否更不普遍。DNA扩增后进行等位基因特异性寡核苷酸连接试验。采用χ2表和Yates校正对等位基因频率进行分析。N291S变异在11.1%的先兆子痫患者中被发现，而在妊娠对照组中为2.9% （p=0.008）。所有D9N的携带者同时也是−93T→G的携带者。D9N/ - 93T→G组合变异在7.1%的先兆子痫患者中发现，而在妊娠对照组中为1.4% （p=0.02）。没有个体同时携带N291S和D9N/−93T→G。因此，18.2%的先兆子痫患者有这些LPL突变中的任何一种，而妊娠对照组的这一比例为4.3%（人口对照组为4.4%）。S447X变异的频率在各组之间没有差异。我们得出结论，LPL基因中N291S或D9N/ - 93T→G组合突变的携带者患先兆子痫的风险显著增加。
Marked dyslipidemia may contribute to endothelial cell dysfunction in pre‐eclampsia. Carriers of N291S or D9N missense mutations in the lipoprotein lipase (LPL) gene exhibit reductions in LPL activity and are predisposed to dyslipidemia and cardiovascular disease. In Caucasians, the D9N variant is in strong linkage disequilibrium with the −93T→G promoter variant. A fourth LPL variant, S447X, is often associated with a beneficial lipid profile. We asked if the N291S and the combination D9N/−93T→G variants are more prevalent, and if the S447X variant is less prevalent, in Caucasian women with pre‐eclampsia as compared with normal pregnancies. DNA amplification was followed by an allele‐specific oligonucleotide ligation assay. Allele frequencies were analyzed with a χ2table and Yates’ correction. The N291S variant was identified in 11.1% of pre‐eclamptics as compared with 2.9% of pregnancy controls (p=0.008). All carriers of D9N were also carriers of −93T→G. The D9N/−93T→G combined variant was found in 7.1% of pre‐eclamptics as compared with 1.4% of pregnancy controls (p=0.02). No individuals were carriers of both N291S and D9N/−93T→G. Thus, 18.2% of pre‐eclamptics had either of these LPL mutations compared with 4.3% of pregnancy controls (and 4.4% of population controls). The frequency of the S447X variant did not differ among groups. We conclude that carriers of N291S or combined D9N/−93T→G mutations in the LPL gene are at substantially increased risk of pre‐eclampsia.