Journal article
A functional polymorphism at the transcriptional initiation site in β2‐glycoprotein I (apolipoprotein H) associated with reduced gene expression and lower plasma levels of β2‐glycoprotein I
European journal of biochemistry, Vol.270(2), pp.230-238
01/2003
DOI: 10.1046/j.1432-1033.2003.03379.x
Abstract
Human β2‐glycoprotein I (β2GPI), also known as apolipoprotein H, has been implicated in haemostasis and the production of anti‐phospholipid antibodies. There is a wide range of interindividual variation in β2GPI plasma levels that is thought to be under genetic control, but its molecular basis remains unknown. To understand the genetic basis of β2GPI variation, we analyzed the 5′ flanking region of the β2GPI gene for mutation detection by DHPLC and identified a point mutation at the transcriptional initiation site (−1C→A) with a carrier frequency of 12.1%. The mutation was associated with significantly lower β2GPI plasma levels (P < 0.0001) and low occurrence of anti‐phospholipid antibodies in lupus patients (4.8% antibody‐positive group vs. 16.6% in the antibody‐negative group; P = 0.019). Northern blot analysis confirmed that the −1C→A mutation was associated with lower mRNA levels and it reduced the reporter (luciferase) gene expression by twofold. Electrophoretic gel mobility shift assay (EMSA) revealed that the −1C→A mutation disrupts the binding for crude hepatic nuclear extracts and purified TFIID. These results suggest that the substitution of C with A at the β2GPI transcriptional initiation site is a causative mutation that affects its gene expression at the transcriptional level and ultimately β2GPI plasma levels and the occurrence of anti‐phospholipid antibodies.
Details
- Title: Subtitle
- A functional polymorphism at the transcriptional initiation site in β2‐glycoprotein I (apolipoprotein H) associated with reduced gene expression and lower plasma levels of β2‐glycoprotein I
- Creators
- Haider Mehdi - Department of Human Genetics, Graduate School of Public Health,Susan Manzi - Department of Medicine andPurnima Desai - Department of Human Genetics, Graduate School of Public Health,Qi Chen - Department of Human Genetics, Graduate School of Public Health,Cara Nestlerode - Department of Human Genetics, Graduate School of Public Health,Franklin Bontempo - Department of Medicine andStephen C. Strom - University of PittsburghReza Zarnegar - University of PittsburghM. Ilyas Kamboh - Department of Human Genetics, Graduate School of Public Health,
- Resource Type
- Journal article
- Publication Details
- European journal of biochemistry, Vol.270(2), pp.230-238
- Publisher
- Blackwell Science Ltd
- DOI
- 10.1046/j.1432-1033.2003.03379.x
- ISSN
- 0014-2956
- eISSN
- 1432-1033
- Number of pages
- 9
- Language
- English
- Date published
- 01/2003
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984360043302771
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