Genetics of apolipoprotein H (beta2-glycoprotein I) and anionic phospholipid binding

M I Kamboh; H Mehdi

doi:10.1177/096120339800700203

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Genetics of apolipoprotein H (beta2-glycoprotein I) and anionic phospholipid binding

Journal article

Peer reviewed

Genetics of apolipoprotein H (beta2-glycoprotein I) and anionic phospholipid binding

M I Kamboh and H Mehdi

Lupus, Vol.7 Suppl 2(2_suppl), pp.S10-13

1998

DOI: 10.1177/096120339800700203

PMID: 9814664

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Abstract

Apolipoprotein H (apoH; also known as beta2-glycoprotein I), is an essential cofactor for the binding of certain antiphospholipid antibodies (APA) to anionic phospholipid. The gene coding for apoH is polymorphic, with the occurrence of several common alleles in the general population. This genetically determined variation can effect the binding of apoH to anionic phospholipids and consequently the production of APA. Our group has identified two common mutations at codons 306 (Cys-->Gly) and 316 (Trp-->Ser) in the fifth domain of apoH which affect the binding of apoH to anionic phospholipids (phosphatidylserine or cardiolipin). ApoH from serum samples homozygous for each of these mutations or compound heterozygotes for both mutations showed no binding with anionic phospholipids on ELISA. In vitro mutagenesis and transient expression of these mutations in COS-1 cells followed by cardiolipin binding studies confirmed that Gly306 and Ser316 are causative mutations. Our data indicate that the fifth domain of apoH is essential for anionic phospholipid binding and genetically determined variation in this domain can affect the production of apoH-dependent APA.

Alleles

Amino Acid Substitution

Animals

Anions

Antiphospholipid Syndrome - genetics

Antiphospholipid Syndrome - immunology

Autoimmune Diseases - genetics

Autoimmune Diseases - immunology

beta 2-Glycoprotein I

Cardiolipins - metabolism

Codon - genetics

COS Cells

Genotype

Glycoproteins - chemistry

Glycoproteins - genetics

Glycoproteins - immunology

Glycoproteins - metabolism

Humans

Phosphatidylserines - metabolism

Phospholipids - chemistry

Phospholipids - immunology

Phospholipids - metabolism

Point Mutation

Polymorphism, Genetic

Protein Binding

Protein Structure, Tertiary

Recombinant Fusion Proteins - metabolism

Details

Title: Subtitle: Genetics of apolipoprotein H (beta2-glycoprotein I) and anionic phospholipid binding
Creators: M I Kamboh - University of Pittsburgh
H Mehdi - University of Pittsburgh
Resource Type: Journal article
Publication Details: Lupus, Vol.7 Suppl 2(2_suppl), pp.S10-13
DOI: 10.1177/096120339800700203
PMID: 9814664
ISSN: 0961-2033
eISSN: 1477-0962
Grant note: HL 54900 / NHLBI NIH HHS
Language: English
Date published: 1998
Academic Unit: Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984359698902771

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15 Times Cited - Web of Science