Influence of LDL receptor gene mutations and the R3500Q mutation of the apoB gene on lipoprotein phenotype of familial hypercholesterolemic patients from a South European population

被引:0
作者
José T Real
Felipe J Chaves
Ismael Ejarque
Ana B García-García
Carmen Valldecabres
Juan F Ascaso
María E Armengod
Rafael Carmena
机构
[1] Service of Endocrinology and Nutrition,Department of Medicine
[2] Hospital Clínico Universitario,undefined
[3] University of Valencia,undefined
[4] Instituto de Investigaciones Citológicas,undefined
[5] Fundación Valenciana de Investigaciones Biomédicas,undefined
来源
European Journal of Human Genetics | 2003年 / 11卷
关键词
heterozygous familial hypercholesterolemia; genetic diagnosis; LDL receptor gene mutations; lipoprotein phenotype; familial ligand-defective apoB 100; R3500Q mutation;
D O I
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学科分类号
摘要
Few data are available on genotype–phenotype interactions among familial hypercholesterolemia (FH) patients in South European populations and there are no data about the influence of R3500Q mutation on lipoprotein phenotype compared to low-density lipoprotein receptor (LDLR) mutations. The objective of the study is to analyze the influence of mutations in the LDLR and apolipoprotein B (apoB) genes on lipoprotein phenotype among subjects clinically diagnosed of FH living in East Spain. In all, 113 FH index patients and 100 affected relatives were studied. Genetic diagnosis was carried out following a protocol based on Southern blot and PCR-SSCP analysis. A total of 118 FH subjects could be classified into three groups according to the type of LDLR mutations (null mutations, missense mutations affecting the ligand binding 3–5 repeat, and missense mutations outside this domain). In addition, the lipoprotein phenotype of these FH groups was compared with 19 heterozygous subjects with familial ligand-defective apoB (FDB), due to R3500Q mutation. FH patients carrying missense mutations affecting the ligand binding repeat 3–5 showed total and LDL cholesterol levels significantly higher than FH patients with missense mutations in other LDLR domains or FDB patients. FH subjects carrying null mutations showed lower high-density lipoprotein cholesterol plasma values compared to FH carrying missense mutations. FDB subjects showed the lowest total and LDL cholesterol plasma values. In conclusion, the type of LDLR gene mutation and R3500Q mutation influences the lipoprotein phenotype of FH population from East Spain.
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页码:959 / 965
页数:6
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共 175 条
[11]  
Haddad L(1995)Is responsiveness to lovastatin in familial hypercholesterolaemia influenced by the specific mutation in the low density lipoprotein receptor gene? Eur J Clin Invest 25 967-973
[12]  
Volh MC(1998)Influence of genotype at the low density lipoprotein receptor gene locus of the clinical phenotype and response to lipid lowering drug therapy in heterozygous familial hypercholesterolemia Atherosclerosis 136 175-185
[13]  
Gaudet D(1993)Mutations of low density lipoprotein receptor gene, variation in plasma cholesterol, and expression of coronary heart disease in homozygous familial hypercholesterolemia Lancet 341 1303-1306
[14]  
Moorjani S(1999)Mutation screening and genotype: phenotype correlation in familial hypercholesterol-emia Atherosclerosis 147 309-316
[15]  
Hoeg JM(1994)Effect on plasma lipid levels of different classes of mutations in the low density lipoprotein receptor gene in patients with familial hypercholesterolemia Arterioscle Thromb 14 1717-1722
[16]  
Ferrières J(2000)Clinical expression of familial hypercholesterolemia in cluster of mutations of the LDL receptor gene that cause a receptor defective or receptor negative phenotype Arterioscle Thromb Vasc Biol 20 e41-e52
[17]  
Lambert J(1999)Manifestaciones clínicas de la hipercolesterolemia familiar en una población mediterránea Med Clin (Barna) 113 521-525
[18]  
Lussier-Cacan S(2001)Large rearrangements of the LDL receptor gene and lipid profile in a Spanish population Eur J Clin Invest 31 309-317
[19]  
Davignon J(2001)Genetic diagnosis of familial hypercholesterolemia in a south European outbreed population: influence of low density lipoprotein (LDL) receptor gene mutations on treatment response to simvastatin in total, LDL and high density lipoprotein cholesterol J Clin Endocrinol Metab 86 4926-4932
[20]  
Kotze MJ(2001)Molecular genetics of familial hypercholesterolemia in Spain: ten novel LDLR mutations and population analysis Hum Mutat 454 1-9