Low-density lipoprotein receptor gene mutation analysis and clinical correlation in Belgian hypercholesterolaemics
It is generally believed that patients with familial hypercholesterolaemia (FH) have a higher cardiovascular risk than hypercholesterolaemics without a defect in the low-density lipoprotein receptor (LDLR) gene. However, no conclusive evidence to support this view has yet been presented. We investig...
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| Veröffentlicht in: | Molecular and cellular probes 2001-12, Vol.15 (6), p.329-336 |
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| creator | Van Gaal, L.F. Peeters, A.V. De Block, C.E.M. de Leeuw, I.H. Thiart, R. Kotze, M.J. |
| description | It is generally believed that patients with familial hypercholesterolaemia (FH) have a higher cardiovascular risk than hypercholesterolaemics without a defect in the low-density lipoprotein receptor (LDLR) gene. However, no conclusive evidence to support this view has yet been presented. We investigated this aspect in Belgian hyperlipidaemics as part of a comprehensive effort to determine the impact of FH in this population. DNA samples of 98 unrelated Belgian patients with a family history of autosomal dominant hypercholesterolaemia were screened for mutations in the LDLR gene, after exclusion of known mutations causing familial defective apolipoprotein B-100 (FDB). Eight of the 22 distinct LDLR gene mutations identified in 27 subjects have not previously been described in other populations. As expected, the mutation-positive patients had a significantly worse lipid profile than the mutation-negative subjects (p |
| doi_str_mv | 10.1006/mcpr.2001.0378 |
| format | Article |
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However, no conclusive evidence to support this view has yet been presented. We investigated this aspect in Belgian hyperlipidaemics as part of a comprehensive effort to determine the impact of FH in this population. DNA samples of 98 unrelated Belgian patients with a family history of autosomal dominant hypercholesterolaemia were screened for mutations in the LDLR gene, after exclusion of known mutations causing familial defective apolipoprotein B-100 (FDB). Eight of the 22 distinct LDLR gene mutations identified in 27 subjects have not previously been described in other populations. As expected, the mutation-positive patients had a significantly worse lipid profile than the mutation-negative subjects (p<0·05), but this did not correlate with clinical cardiovascular status. In conclusion, the presence of a mutation in the LDLR gene was not a reliable predictor of cardiovascular risk in the hyperlipidaemic subjects included in this study. However, it is possible that prolonged exposure to the high levels of LDL cholesterol in genetically proven FH patients will in future cause a higher incidence of coronary heart disease. Our data may reflect the genetic heterogeneity of inherited hypercholesterolaemia, recently shown to be caused by several major genes.</description><identifier>ISSN: 0890-8508</identifier><identifier>EISSN: 1096-1194</identifier><identifier>DOI: 10.1006/mcpr.2001.0378</identifier><identifier>PMID: 11851376</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Belgium ; Child ; Coronary Disease - etiology ; Coronary Disease - genetics ; familial hypercholesterolaemia, LDL receptor gene, cardiovascular disease ; Female ; Humans ; Hypercholesterolemia - genetics ; Hyperlipoproteinemia Type II - genetics ; Male ; Middle Aged ; Mutation ; Receptors, LDL - genetics ; Regression Analysis ; Risk Factors</subject><ispartof>Molecular and cellular probes, 2001-12, Vol.15 (6), p.329-336</ispartof><rights>2001 Academic Press</rights><rights>Copyright 2001 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c340t-a62482ca3e48b7df2b13c5ce991ef42fb79ae01b00f1a0848b406347ad0dffc83</citedby><cites>FETCH-LOGICAL-c340t-a62482ca3e48b7df2b13c5ce991ef42fb79ae01b00f1a0848b406347ad0dffc83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/mcpr.2001.0378$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11851376$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Van Gaal, L.F.</creatorcontrib><creatorcontrib>Peeters, A.V.</creatorcontrib><creatorcontrib>De Block, C.E.M.</creatorcontrib><creatorcontrib>de Leeuw, I.H.</creatorcontrib><creatorcontrib>Thiart, R.</creatorcontrib><creatorcontrib>Kotze, M.J.</creatorcontrib><title>Low-density lipoprotein receptor gene mutation analysis and clinical correlation in Belgian hypercholesterolaemics</title><title>Molecular and cellular probes</title><addtitle>Mol Cell Probes</addtitle><description>It is generally believed that patients with familial hypercholesterolaemia (FH) have a higher cardiovascular risk than hypercholesterolaemics without a defect in the low-density lipoprotein receptor (LDLR) gene. However, no conclusive evidence to support this view has yet been presented. We investigated this aspect in Belgian hyperlipidaemics as part of a comprehensive effort to determine the impact of FH in this population. DNA samples of 98 unrelated Belgian patients with a family history of autosomal dominant hypercholesterolaemia were screened for mutations in the LDLR gene, after exclusion of known mutations causing familial defective apolipoprotein B-100 (FDB). Eight of the 22 distinct LDLR gene mutations identified in 27 subjects have not previously been described in other populations. As expected, the mutation-positive patients had a significantly worse lipid profile than the mutation-negative subjects (p<0·05), but this did not correlate with clinical cardiovascular status. In conclusion, the presence of a mutation in the LDLR gene was not a reliable predictor of cardiovascular risk in the hyperlipidaemic subjects included in this study. However, it is possible that prolonged exposure to the high levels of LDL cholesterol in genetically proven FH patients will in future cause a higher incidence of coronary heart disease. Our data may reflect the genetic heterogeneity of inherited hypercholesterolaemia, recently shown to be caused by several major genes.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Belgium</subject><subject>Child</subject><subject>Coronary Disease - etiology</subject><subject>Coronary Disease - genetics</subject><subject>familial hypercholesterolaemia, LDL receptor gene, cardiovascular disease</subject><subject>Female</subject><subject>Humans</subject><subject>Hypercholesterolemia - genetics</subject><subject>Hyperlipoproteinemia Type II - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Receptors, LDL - genetics</subject><subject>Regression Analysis</subject><subject>Risk Factors</subject><issn>0890-8508</issn><issn>1096-1194</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kD1PwzAQhi0EoqWwMqJMbCl3SZo4I1R8SZVYYLYc59IaOXawU1D_Pa5aiYnpbnjeV3cPY9cIcwQo73o1-HkGgHPIK37Cpgh1mSLWxSmbAq8h5QvgE3YRwicA1AXwczZB5AvMq3LK_Mr9pC3ZoMddYvTgBu9G0jbxpGgYnU_WZCnpt6MctbOJtNLsgg5xaRNltNVKmkQ578kciJh9ILPW0iab3UBebZyhMJJ3RlKvVbhkZ500ga6Oc8Y-nh7fly_p6u35dXm_SlVewJjKMit4pmROBW-qtssazNVCUV0jdUXWNVUtCbAB6FACj1ABZV5UsoW26xTPZ-z20Btf-trGE0SvgyJjpCW3DaLCjGOFiwjOD6DyLgRPnRi87qXfCQSxtyz2lsXesthbjoGbY_O26an9w49aI8APAMX_vjV5EZQmq6jV0esoWqf_6_4FP76Pdw</recordid><startdate>20011201</startdate><enddate>20011201</enddate><creator>Van Gaal, L.F.</creator><creator>Peeters, A.V.</creator><creator>De Block, C.E.M.</creator><creator>de Leeuw, I.H.</creator><creator>Thiart, R.</creator><creator>Kotze, M.J.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20011201</creationdate><title>Low-density lipoprotein receptor gene mutation analysis and clinical correlation in Belgian hypercholesterolaemics</title><author>Van Gaal, L.F. ; Peeters, A.V. ; De Block, C.E.M. ; de Leeuw, I.H. ; Thiart, R. ; Kotze, M.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c340t-a62482ca3e48b7df2b13c5ce991ef42fb79ae01b00f1a0848b406347ad0dffc83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Belgium</topic><topic>Child</topic><topic>Coronary Disease - etiology</topic><topic>Coronary Disease - genetics</topic><topic>familial hypercholesterolaemia, LDL receptor gene, cardiovascular disease</topic><topic>Female</topic><topic>Humans</topic><topic>Hypercholesterolemia - genetics</topic><topic>Hyperlipoproteinemia Type II - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Receptors, LDL - genetics</topic><topic>Regression Analysis</topic><topic>Risk Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Van Gaal, L.F.</creatorcontrib><creatorcontrib>Peeters, A.V.</creatorcontrib><creatorcontrib>De Block, C.E.M.</creatorcontrib><creatorcontrib>de Leeuw, I.H.</creatorcontrib><creatorcontrib>Thiart, R.</creatorcontrib><creatorcontrib>Kotze, M.J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular and cellular probes</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Van Gaal, L.F.</au><au>Peeters, A.V.</au><au>De Block, C.E.M.</au><au>de Leeuw, I.H.</au><au>Thiart, R.</au><au>Kotze, M.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low-density lipoprotein receptor gene mutation analysis and clinical correlation in Belgian hypercholesterolaemics</atitle><jtitle>Molecular and cellular probes</jtitle><addtitle>Mol Cell Probes</addtitle><date>2001-12-01</date><risdate>2001</risdate><volume>15</volume><issue>6</issue><spage>329</spage><epage>336</epage><pages>329-336</pages><issn>0890-8508</issn><eissn>1096-1194</eissn><abstract>It is generally believed that patients with familial hypercholesterolaemia (FH) have a higher cardiovascular risk than hypercholesterolaemics without a defect in the low-density lipoprotein receptor (LDLR) gene. However, no conclusive evidence to support this view has yet been presented. We investigated this aspect in Belgian hyperlipidaemics as part of a comprehensive effort to determine the impact of FH in this population. DNA samples of 98 unrelated Belgian patients with a family history of autosomal dominant hypercholesterolaemia were screened for mutations in the LDLR gene, after exclusion of known mutations causing familial defective apolipoprotein B-100 (FDB). Eight of the 22 distinct LDLR gene mutations identified in 27 subjects have not previously been described in other populations. As expected, the mutation-positive patients had a significantly worse lipid profile than the mutation-negative subjects (p<0·05), but this did not correlate with clinical cardiovascular status. In conclusion, the presence of a mutation in the LDLR gene was not a reliable predictor of cardiovascular risk in the hyperlipidaemic subjects included in this study. However, it is possible that prolonged exposure to the high levels of LDL cholesterol in genetically proven FH patients will in future cause a higher incidence of coronary heart disease. Our data may reflect the genetic heterogeneity of inherited hypercholesterolaemia, recently shown to be caused by several major genes.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>11851376</pmid><doi>10.1006/mcpr.2001.0378</doi><tpages>8</tpages></addata></record> |
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| subjects | Adolescent Adult Aged Belgium Child Coronary Disease - etiology Coronary Disease - genetics familial hypercholesterolaemia, LDL receptor gene, cardiovascular disease Female Humans Hypercholesterolemia - genetics Hyperlipoproteinemia Type II - genetics Male Middle Aged Mutation Receptors, LDL - genetics Regression Analysis Risk Factors |
| title | Low-density lipoprotein receptor gene mutation analysis and clinical correlation in Belgian hypercholesterolaemics |
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