Lade J A, Moses E K, Guo G, Wilton A N, Grehan M, Cooper D W, Brennecke S P
Department of Perinatal Medicine, Royal Women's Hospital, Carlton, Victoria, Australia.
Hypertens Pregnancy. 1999;18(1):81-93. doi: 10.3109/10641959909009613.
To investigate the endothelial cell nitric oxide synthase (eNOS) gene as a candidate for susceptibility to preeclampsia.
Twenty-six Australian families containing 11 eclamptics, 59 severe preeclamptics, and 27 mild preeclamptics were used to test for linkage between the eNOS gene region and preeclampsia. Two microsatellite markers (D7S483 and D7S505) in the proximity of the eNOS gene were used.
Logarithm of odds (LOD) scores were used to examine the cosegregation of alleles with the disease under a variety of inheritance models. Model-independent analysis, affected pedigree member method (AFFPED), and pairwise haplotype sharing between affected sibs were also used.
Two-point LOD score analysis gave no evidence of linkage between preeclampsia and two markers in close proximity to the eNOS gene (LOD scores < 1) for any of the inheritance models investigated, with no evidence of heterogeneity between pedigrees. The AFFPED and the pairwise haplotype sharing test on affected sibs also gave no evidence of linkage (p-values > 0.05).
This study provides no evidence for linkage between two markers in close proximity to the eNOS gene and preeclampsia in these families. These results do not support the recent suggestion that eNOS could be a familial pregnancy-induced hypertension gene (Arngrimsson R, et al., Am J Hum Genet 1997;61:354-62). Distinguishing preeclampsia from other hypertensive disorders in pregnancy is difficult. Hypertension appears to be a consequence, rather than a primary cause of preeclampsia. Given the vasodilatory role of the eNOS gene product, it is possible that the linkage recently reported for eNOS reflects its relationship with hypertension rather than preeclampsia.
研究内皮细胞一氧化氮合酶（eNOS）基因作为子痫前期易感性候选基因的可能性。
选取26个澳大利亚家庭，其中包括11例子痫患者、59例重度子痫前期患者和27例轻度子痫前期患者，用于检测eNOS基因区域与子痫前期之间的连锁关系。使用了位于eNOS基因附近的两个微卫星标记（D7S483和D7S505）。
采用优势对数（LOD）评分来检验在各种遗传模型下等位基因与疾病的共分离情况。还使用了与模型无关的分析、受累家系成员法（AFFPED）以及受累同胞之间的成对单倍型共享分析。
两点LOD评分分析未发现子痫前期与eNOS基因附近的两个标记之间存在连锁关系（LOD评分<1），对于所研究的任何遗传模型均如此，且家系之间不存在异质性证据。对受累同胞进行的AFFPED和成对单倍型共享检验也未发现连锁关系（p值>0.05）。
本研究未发现这些家庭中eNOS基因附近的两个标记与子痫前期之间存在连锁关系。这些结果不支持最近提出的eNOS可能是家族性妊娠高血压基因的观点（Arngrimsson R等人，《美国人类遗传学杂志》1997年；61:354 - 62）。区分子痫前期与妊娠期间的其他高血压疾病很困难。高血压似乎是子痫前期的一个后果，而非主要原因。鉴于eNOS基因产物的血管舒张作用，最近报道的eNOS连锁关系可能反映了其与高血压的关系，而非与子痫前期的关系。
