Identification of apolipoprotein H mutations and their diagnostic uses
AssigneeUniversity of Pittsburgh
InventorsM. Ilyas Kamboh, Dharambir K. Sanghera, Susan Manzi
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Abstract
Structural mutations in the fifth domain of apolipoprotein H have been identified which affect phospholipid binding and which predict protection from systemic lupus erythematosis which can be used in genetic analysis.
Claims26
A method to determine the presence or absence of a missense mutation at codon 306 of exon 7 of the apolipoprotein H gene in an individual wherein said missense mutation protects said individual against the occurrence of systemic lupus erythematosus, comprising the steps of:
- a) obtaining genomic DNA from said individual;
- b) amplifying said genomic DNA with a primer pair for exon 7 of the apolipoprotein H gene;
- and
- c) determining the presence or absence of a missense mutation at codon 306 of exon 7 of the apolipoprotein H gene from the codon TGC to GGC.
A method to determine the presence or absence of missense mutations in the fifth domain apolipoprotein H gene at codon 306 (TGC→GGC) and codon 316 (TGG→TCG) of an individual that render apolipoprotein H protein unable to bind to negatively charged phospholipid, comprising the steps of:
- a) obtaining genomic DNA from said individual;
- b) amplifying said genomic DNA with a primer pair for exon 7 for codon 306;
- c) amplifying said genomic DNA with a primer pair for exon 8 for codon 316;
- and
- d) determining the presence or absence of said mutations at codon 306 of exon 7 and codon 316 of exon 8 in the fifth domain of said apolipoprotein H gene.
A method to determine the likelihood of an individual producing antiphospholipid autoantibodies and subsequently becoming afflicted with related thrombotic disorders comprising:
- a) obtaining a sample of genomic DNA from said individual;
- and
- b) detecting the presence or absence of missense mutations in the fifth domain of apolipoprotein H gene from said individual that preclude apolipoprotein H protein from binding to negatively charged phospholipid wherein the presence of said missense mutations is indicative of a dercreased likelihood of the the individual producing antiphospholipid autoantibodies.
A method of determining the likelihood of an individual being protected against the occurrence of systemic lupus erythematosus, comprising:
- a) obtaining a sample of genomic DNA from said individual;
- and
- b) detecting the presence or absence of a missense mutation at codon 306 in the fifth domain of apolipoprotein H which causes the substitution Cys-306 by Gly-306 whereby the presence of said missense mutation indicates the likelihood of said individual being protected against the occurrence of systemic lupus erythematosus.
A kit for detection of the presence or absence of mutations in the human apolipoprotein H gene in an individual at codons 306 and 316, comprising:
- at least one pair of amplification primers for amplification of each of said mutations, wherein said amplification primers for codon 306 comprise APOH 2, 5′-GTGTAGGTGTACTCATCTACTGTG-3′ (SEQ ID NO:
- 1), and APOH 9, 5′-CAAGTGGGAGTCCTAGCTAA-3′ (SEQ ID NO:
- 3), and said amplification primers for codon 316 comprise APOH 10, 5′-TTGTTCCCTTAGAATGTTTAT-3′ (SEQ ID NO:
- 4), and APOH 5, 5′-TGGATGAACAAGAAACAAGTG-3′ (SEQ ID NO:
- 2).
Dependencies are inferred from the claim text.