ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04193.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04194.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04195.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

An emerging challenge facing those who are concerned about the efficacy of public health programs is to understand how information from the DNA revolution might be used to improve our ability to predict the initiation, progression and severity of a common disease having a complex multifactorial etiology. In the course of research to evaluate the role of information about DNA, combinations of genome types and environmental exposures that predispose to disease will be identified. Such information is expected to be useful in efforts to identify individuals and families at higher risk of disease and to predict their responses to a proposed therapy. This paper begins with a discussion of the features of a realistic biological model for the study of a common multifactorial disease. We present evidence for the complexity in the relationship between genome type variation and variation in risk of coronary artery disease (CAD) and review the preliminary results of our studies to determine whether information about genome type variation can improve our ability to predict the distribution of CAD among individuals in the population at large. Such studies make it apparent that new analytical strategies are necessary to deal with the plethora of genome type information available for the evaluation of risk of a common disease like CAD. This shift in the research paradigm will build upon new strategies to understand the organization of natural systems that are coming from outside the mainstream of genetic research.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04196.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04197.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04198.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Lp(a) is an LDL‐like lipoprotein that is a major inherited risk factor for atherosclerosis. It is distinguished from Lp(a) by the addition of apolipoprotein(a). The gene structure of apolipoprotein(a) is homologous to plasminogen, and competition with plasminogen activity may account for some of the pathophysiology associated with Lp(a). Six highly related genes have now been identified, and at least four are found in close proximity in overlapping genomic clones. Studies have begun on the regulation of apolipoprotein (a) gene expression, and the human apolipoprotein(a) gene has been inserted into transgenic mice, where it leads to the development of arterial lesion

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04199.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The size polymorphism of Lp(a) is well recognized. It is now apparent that there is an additional polymorphism resulting from mutations occurring at the kringle level. One of these mutations involves a trp72 to arg substitution in apo(a) kringle type 10 and is attended by a defective binding of Lp(a) to immobilized lysine/fibrin. Other mutations affecting the other amino acids of the “lysine‐binding pocket” may have similar functional consequences and may be important at the clinical level in terms of thromboge

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04200.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Lp(a) lipoprotein [Lp(a)] was found in previous studies to be independently associated with early atherosclerosis and its sequelae. Lp(a)in vitrobound to glucosaminoglycans and was easily aggregated at physiological Ca2+concentration, and small Lp(a) aggregates were phagocytosed by macrophages. Lp(a) was also found to be related to carbohydrate metabolism, and increased Lp(a) levels have been described in diabetic patients with clinical complications and were recently found in rheumathoid arthritis patients. In this study of nondiabetic male patients with documented CAD before 50 years of age and controls, a significant correlation was found between Lp(a) and IGF‐1 levels. HLA class II DR13 (DR6) was more frequent and DR15 (DR2) was less frequent in patients than in controls. The calculated relative risk for CAD was 4.0 for DR17 (DR3), but the difference was not significant. These differences seem to be related to high Lp(a) levels. It is suggested that phagocytosis of preferably Lp(a) aggregates can induce an immunological tissue response that may contribute in the pathogenesis of Lp(a)‐associated diseases and may be more prominent in combination with some inherited HLA class II haplotypes. Probably due to sex hormone effects, the association may be most pronounced in young males and in older fema

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04201.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

We report on a woman with an Lp(a) lipoprotein level above the 99th centile of the population distribution of concentrations, who at the age of 43 had had deep vein thrombosis causing a pulmonary embolus and whose brother, who also had a very high level, had suffered a cerebral infarction at the age of 43. She had given birth to three children, all with very low birth weight, one of whom died when 3 months old. The placentas had been small and ischemic. The concurrence of a very high Lp(a) lipoprotein level, familial thromboembolic disease and recurrent placental ischemia with delivery of children with low birth weight suggests the possibility that a very high Lp(a) lipoprotein concentration may predispose to placental insufficiency, presumably arising from pathological changes in maternal uterine vessels in the placental bed. If confirmed, a very high Lp(a) lipoprotein level may be a factor to consider in women who have repeated pregnancies with placental insufficiency and who give birth to children with low birth weight.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04202.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY