COMPLEX SEGREGATION ANALYSIS PROVIDES EVIDENCE FOR A MAJOR GENE ACTING ON SERUM TRIGLYCERIDE LEVELS IN 55 BRITISH FAMILIES WITH FAMILIAL COMBINED HYPERLIPIDEMIA

被引:66
作者
CULLEN, P [1 ]
FARREN, B [1 ]
SCOTT, J [1 ]
FARRALL, M [1 ]
机构
[1] HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,MRC,MOLEC MED GRP,LONDON W12 0NN,ENGLAND
来源
ARTERIOSCLEROSIS AND THROMBOSIS | 1994年 / 14卷 / 08期
关键词
COMBINED HYPERLIPIDEMIA; GENETICS; TYPE IIB HYPERLIPOPROTEINEMIA;
D O I
10.1161/01.ATV.14.8.1233
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Familial combined hyperlipidemia (FCHL) was first described as an autosomal dominant inherited trait with primary action on triglyceride levels and secondary effects on cholesterol metabolism. This conclusion has since been questioned by several groups despite subsequent supportive biochemical and metabolic studies. To reexplore the genetics of FCHL, we assembled 55 families from the United Kingdom comprising 559 persons ascertained through probands with both hypercholesterolemia and hypertriglyceridemia. The results of univariate complex segregation analysis were consistent with a major gene acting on triglyceride and explaining two thirds of the genetic variability and 20% of the phenotypic variance in triglyceride levels. Univariate analysis did not identify a major genetic component acting on cholesterol levels. Bivariate segregation analysis rejected a major gene model. We also reexamined the original FCHL pedigrees collected by Goldstein et al and obtained results similar to those in the UK families. The prospects for mapping putative major genes determining triglyceride levels in FCHL patients by linkage analysis are discussed.
引用
收藏
页码:1233 / 1249
页数:17
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