Detection of variability in apo(a) gene transcription regulatory sequences using the DGGE method
Increased lipoprotein(a), Lp(a), concentration is an independent risk factor for premature atherosclerosis. Apolipoprotein(a), apo(a), determines properties of the lipoprotein and its production rate is the limiting step in Lp(a) particle formation. Subjects covering the whole range of Lp(a) concent...
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| Published in | Clinica chimica acta Vol. 376; no. 1-2; pp. 77 - 81 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.02.2007
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0009-8981 1873-3492 |
| DOI | 10.1016/j.cca.2006.07.016 |
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| Abstract | Increased lipoprotein(a), Lp(a), concentration is an independent risk factor for premature atherosclerosis. Apolipoprotein(a), apo(a), determines properties of the lipoprotein and its production rate is the limiting step in Lp(a) particle formation.
Subjects covering the whole range of Lp(a) concentration were separated into quintiles. A randomly chosen sample from each quintile was derived, there being a total number of 713 individuals. The DGGE method was used to scan the known transcription regulatory regions of apo(a) gene (promoter; DHII and DHIII enhancers) for variability and its distribution across quintiles.
Besides 5 previously reported nucleotide substitutions (+121 G>A; +93 C>T; −1712 G>T; −1617 C>A; −1230 A>G) 16 unreported rare sequence variants were detected. All polymorphic variants were distributed throughout the quintiles with several significant differences. The novel +62 C variant was found only among individuals with Lp(a) levels over 16 mg/dl.
The apo(a) gene transcription regulatory regions were not revealed to be extremely polymorphic. However, we should consider a combined effect of all polymorphic sites from the whole apo(a) gene locus, including the apo(a) gene length polymorphism, when dealing with high population variability of Lp(a) levels. |
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| AbstractList | Increased lipoprotein(a), Lp(a), concentration is an independent risk factor for premature atherosclerosis. Apolipoprotein(a), apo(a), determines properties of the lipoprotein and its production rate is the limiting step in Lp(a) particle formation.BACKGROUNDIncreased lipoprotein(a), Lp(a), concentration is an independent risk factor for premature atherosclerosis. Apolipoprotein(a), apo(a), determines properties of the lipoprotein and its production rate is the limiting step in Lp(a) particle formation.Subjects covering the whole range of Lp(a) concentration were separated into quintiles. A randomly chosen sample from each quintile was derived, there being a total number of 713 individuals. The DGGE method was used to scan the known transcription regulatory regions of apo(a) gene (promoter; DHII and DHIII enhancers) for variability and its distribution across quintiles.METHODSSubjects covering the whole range of Lp(a) concentration were separated into quintiles. A randomly chosen sample from each quintile was derived, there being a total number of 713 individuals. The DGGE method was used to scan the known transcription regulatory regions of apo(a) gene (promoter; DHII and DHIII enhancers) for variability and its distribution across quintiles.Besides 5 previously reported nucleotide substitutions (+121 G>A; +93 C>T; -1712 G>T; -1617 C>A; -1230 A>G) 16 unreported rare sequence variants were detected. All polymorphic variants were distributed throughout the quintiles with several significant differences. The novel +62 C variant was found only among individuals with Lp(a) levels over 16 mg/dl.RESULTSBesides 5 previously reported nucleotide substitutions (+121 G>A; +93 C>T; -1712 G>T; -1617 C>A; -1230 A>G) 16 unreported rare sequence variants were detected. All polymorphic variants were distributed throughout the quintiles with several significant differences. The novel +62 C variant was found only among individuals with Lp(a) levels over 16 mg/dl.The apo(a) gene transcription regulatory regions were not revealed to be extremely polymorphic. However, we should consider a combined effect of all polymorphic sites from the whole apo(a) gene locus, including the apo(a) gene length polymorphism, when dealing with high population variability of Lp(a) levels.CONCLUSIONThe apo(a) gene transcription regulatory regions were not revealed to be extremely polymorphic. However, we should consider a combined effect of all polymorphic sites from the whole apo(a) gene locus, including the apo(a) gene length polymorphism, when dealing with high population variability of Lp(a) levels. Increased lipoprotein(a), Lp(a), concentration is an independent risk factor for premature atherosclerosis. Apolipoprotein(a), apo(a), determines properties of the lipoprotein and its production rate is the limiting step in Lp(a) particle formation. Subjects covering the whole range of Lp(a) concentration were separated into quintiles. A randomly chosen sample from each quintile was derived, there being a total number of 713 individuals. The DGGE method was used to scan the known transcription regulatory regions of apo(a) gene (promoter; DHII and DHIII enhancers) for variability and its distribution across quintiles. Besides 5 previously reported nucleotide substitutions (+121 G>A; +93 C>T; -1712 G>T; -1617 C>A; -1230 A>G) 16 unreported rare sequence variants were detected. All polymorphic variants were distributed throughout the quintiles with several significant differences. The novel +62 C variant was found only among individuals with Lp(a) levels over 16 mg/dl. The apo(a) gene transcription regulatory regions were not revealed to be extremely polymorphic. However, we should consider a combined effect of all polymorphic sites from the whole apo(a) gene locus, including the apo(a) gene length polymorphism, when dealing with high population variability of Lp(a) levels. Increased lipoprotein(a), Lp(a), concentration is an independent risk factor for premature atherosclerosis. Apolipoprotein(a), apo(a), determines properties of the lipoprotein and its production rate is the limiting step in Lp(a) particle formation. Subjects covering the whole range of Lp(a) concentration were separated into quintiles. A randomly chosen sample from each quintile was derived, there being a total number of 713 individuals. The DGGE method was used to scan the known transcription regulatory regions of apo(a) gene (promoter; DHII and DHIII enhancers) for variability and its distribution across quintiles. Besides 5 previously reported nucleotide substitutions (+121 G>A; +93 C>T; −1712 G>T; −1617 C>A; −1230 A>G) 16 unreported rare sequence variants were detected. All polymorphic variants were distributed throughout the quintiles with several significant differences. The novel +62 C variant was found only among individuals with Lp(a) levels over 16 mg/dl. The apo(a) gene transcription regulatory regions were not revealed to be extremely polymorphic. However, we should consider a combined effect of all polymorphic sites from the whole apo(a) gene locus, including the apo(a) gene length polymorphism, when dealing with high population variability of Lp(a) levels. |
| Author | Kebrdlová, Věra Zlatohlávek, Lukáš Češka, Richard Zídková, Kateřina |
| Author_xml | – sequence: 1 givenname: Kateřina surname: Zídková fullname: Zídková, Kateřina email: kzidk@lf1.cuni.cz organization: 3rd Medical Department, 1st Faculty of Medicine and General Teaching Hospital, Charles University in Prague, Prague 12808, Czech Republic – sequence: 2 givenname: Věra surname: Kebrdlová fullname: Kebrdlová, Věra organization: Institute of Biology and Medical Genetics, 1st Faculty of Medicine, Charles University in Prague, Prague 12800, Czech Republic – sequence: 3 givenname: Lukáš surname: Zlatohlávek fullname: Zlatohlávek, Lukáš organization: 3rd Medical Department, 1st Faculty of Medicine and General Teaching Hospital, Charles University in Prague, Prague 12808, Czech Republic – sequence: 4 givenname: Richard surname: Češka fullname: Češka, Richard organization: 3rd Medical Department, 1st Faculty of Medicine and General Teaching Hospital, Charles University in Prague, Prague 12808, Czech Republic |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/16916503$$D View this record in MEDLINE/PubMed |
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| Title | Detection of variability in apo(a) gene transcription regulatory sequences using the DGGE method |
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