Low density lipoprotein receptor mutations in a selected population of individuals with moderate hypercholesterolemia

被引:17
作者
Arca, M [1 ]
Jokinen, E [1 ]
机构
[1] Univ Texas, SW Med Ctr, Dept Mol Genet, Dallas, TX 75235 USA
关键词
LDL-receptor; hypercholesterolemia; familial hypercholesterolemia;
D O I
10.1016/S0021-9150(97)00210-4
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To evaluate mutations in the low density lipoprotein receptor (LDL-R) gene in moderate primary hypercholesterolemia, a combination of polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and direct sequencing, was used to screen the LDL-R gene in a selected population of 82 unrelated individuals with moderate elevation of plasma LDL-C [mean 4.55 +/- 0.55 mmol/l (176.4 +/- 21.6 mg/dl)]. Four subjects (5%) were found to be heterozygotes for missense mutations in the LDL-R gene. These mutations were located in four different exons (exons 6, 7 15 and 17) and all alters highly conserved residues of LDL-R protein. None of these mutations were detected in 79 normocholesterolemic individuals. The mutation in exon 15 (T705I) was previously reported in a compound heterozygote for familial hypercholesterolemia (FH). In the proband carrying the mutation in exon 17 (R793Q), an in vivo LDL turnover study was performed and it demonstrated a reduction of LDL catabolism. These findings demonstrate that mutations in the LDL-R may occur in primary moderate hypercholesterolemia. They also extend the concept that some FH patients may present with a mild phenotype. (C) 1998 Elsevier Science Ireland Ltd.
引用
收藏
页码:187 / 194
页数:8
相关论文
共 27 条
[21]   FAMILIAL HYPERCHOLESTEROLEMIA WITH NORMAL CHOLESTEROL IN OBLIGATE HETEROZYGOTES .1. [J].
NORA, JJ ;
LORTSCHER, RM ;
SPANGLER, RD ;
BILHEIMER, DW .
AMERICAN JOURNAL OF MEDICAL GENETICS, 1985, 22 (03) :585-591
[22]   RAPID AND SENSITIVE DETECTION OF POINT MUTATIONS AND DNA POLYMORPHISMS USING THE POLYMERASE CHAIN-REACTION [J].
ORITA, M ;
SUZUKI, Y ;
SEKIYA, T ;
HAYASHI, K .
GENOMICS, 1989, 5 (04) :874-879
[23]  
PEDERSEN JC, 1988, CLIN GENET, V34, P306
[24]  
SAINTJORE B, 1993, HUM GENET, V91, P511
[25]   THE SENSITIVITY OF SINGLE-STRAND CONFORMATION POLYMORPHISM ANALYSIS FOR THE DETECTION OF SINGLE BASE SUBSTITUTIONS [J].
SHEFFIELD, VC ;
BECK, JS ;
KWITEK, AE ;
SANDSTROM, DW ;
STONE, EM .
GENOMICS, 1993, 16 (02) :325-332
[26]   4 DNA POLYMORPHISMS IN THE LDL RECEPTOR GENE - THEIR GENETIC-RELATIONSHIP AND USE IN THE STUDY OF VARIATION AT THE LDL RECEPTOR LOCUS [J].
TAYLOR, R ;
JEENAH, M ;
SEED, M ;
HUMPHRIES, S .
JOURNAL OF MEDICAL GENETICS, 1988, 25 (10) :653-659
[27]   METABOLIC BASIS OF PRIMARY HYPERCHOLESTEROLEMIA [J].
VEGA, GL ;
DENKE, MA ;
GRUNDY, SM .
CIRCULATION, 1991, 84 (01) :118-128