A genome-wide scan reveals a maternal susceptibility locus for pre-eclampsia on chromosome 2p13.

Pre-eclampsia is a common and serious disease and a major cause of maternal and infant mortality. Antenatal care systems world-wide screen for signs of the disease such as hypertension and proteinuria. Unlike most other human disorders it impacts two individuals, the mother and the child, both of whom can be severely affected. The pathophysiology of the disorder is incompletely understood, but familial clustering of the disease is apparent. Here we report the results of a genome-wide screen of Icelandic families representing 343 affected women. Including those patients with non-proteinuric pre-eclampsia (gestational hypertension), proteinuric pre-eclampsia and eclampsia, we detected a significant locus on 2p13 with a lod score of 4.70 (single point P < 3.49 x 10(-6)). This is the first reported locus for pre-eclampsia meeting the criteria for genome-wide significance.

Evidence for a familial pregnancy-induced hypertension locus in the eNOS-gene region.

Pregnancy-induced hypertension may be regarded as a manifestation of endothelial-cell dysfunction. The role of the eNOS gene in the development of a familial pregnancy-induced hypertension was evaluated by analysis of linkage among affected sisters and in multiplex families (n = 50). Markers from a 4-cM region encoding the eNOS gene showed distortion from the expected allele sharing among affected sisters (P = .001-.05), and the statistic obtained from the multilocus application of the affected-pedigree-member method also showed distortion (T[f(P)=sqrt(P)] = 3.53; P < .001). A LOD score of 3.36 was obtained for D7S505 when a best-fitting model derived from genetic epidemiological data was used, and LOD scores of 2.54-4.03 were obtained when various other genetic models were used. Estimates of recombination rate, rather than maximum LOD-score values, were affected by changes in the genetic parameters. The transmission-disequilibrium test, a model-free estimate of linkage, showed strongest association and linkage with a microsatellite within intron 13 of the eNOS gene (P = .005). These results support the localization of a familial pregnancy-induced hypertension-susceptibility locus in the region of chromosome 7q36 encoding the eNOS gene.

Predictive value of apolipoproteins in a prospective survey of coronary artery disease in men.

Some studies have suggested that measurements of apolipoproteins may be valuable in the clinical assessment of susceptibility to coronary artery disease, over and above the lipoprotein lipids. Only a few of these studies have been prospective in nature and further knowledge is therefore needed to clarify the issue. The independent prognostic value of apolipoproteins (apo-B, apo-AI and apo[a]) with regard to coronary artery disease was estimated from a prospective survey among 1,332 randomly selected Icelandic men, aged 45 to 72 years, participating in a health survey from 1979 to 1981. The group was followed for 8.6 years, and during that period 104 men had fatal or nonfatal myocardial infarction. The Cox's proportional hazards model was used to estimate the significance of independent variables. The results of multivariate analysis showed that apo(a) was a significant independent risk factor (odds ratio 1.22 for 1 SD), but apo-AI was a stronger negative risk factor (odds ratio 0.70 for 1 SD). Apo-B was a highly significant risk factor in a univariate analysis, but not in a multivariate analysis when serum cholesterol was included. Previous population surveys in Iceland have confirmed the importance of cigarette smoking, cholesterol, triglycerides and blood pressure as risk factors for coronary artery disease. The present results illustrate additional importance of apo-AI and apo(a) concentrations in predicting coronary artery disease among Icelandic men, whereas apo-B did not contribute anything further to the prediction than serum total cholesterol.