Peroxisome proliferator-activated receptor alpha and disorders of lipid metabolism

Abstract

The complete genomic structure of the peroxisome proliferator-activated receptor alpha gene is described. Also described are the identification of novel single nucleotide polymorphisms and association with higher plasma LDL-cholesterol and total and LDL-apolipoprotein B concentrations.

What is claimed is:  
     
         1 . An isolated nucleic acid molecule comprising all or a portion of at least 10 contiguous nucleotides of the PPARα nucleotide sequence, as exemplified by SEQ ID NO: 1, or an allelic varient thereof, wherein the isolated nucleic acid molecule comprises a polymorphic site at the first nucleotide position of codon 162 of the PPARα gene which is occupied by a guanine (G), and complements of said isolated nucleic acid molecule.  
     
     
         2 . An expression vector comprising the isolated nucleic acid molecule of  claim 1 .  
     
     
         3 . A host cell comprising the expression vector of  claim 2 .  
     
     
         4 . An oligonucleotide microarray having immobilized thereon a plurality of probes, wherein at least one of said probes is specific for the isolated nucleic acid molecule comprising all or a portion of at least 10 contiguous nucleotides of the PPARα nucleotide sequence, as exemplified by SEQ ID NO: 1, or an allelic varient thereof, wherein the isolated nucleic acid molecule comprises a polymorphic site at the first nucleotide position of codon 162 of the PPARα gene which is occupied by a guanine (G), and wherein said probe comprises the polymorphic site.  
     
     
         5 . An isolated nucleic acid molecule comprising all or a portion of at least 10 contiguous nucleotides of the PPARα nucleotide sequence, as exemplified by SEQ ID NO: 1, or an allelic varient thereof, wherein the isolated nucleic acid molecule comprises a polymorphic site at nucleotide position 696 of the PPARα gene which is occupied by a guanine (G), and complements of said isolated nucleic acid molecule.  
     
     
         6 . An expression vector comprising the isolated nucleic acid molecule of  claim 5 .  
     
     
         7 . A host cell comprising the expression vector of  claim 6 .  
     
     
         8 . An oligonucleotide microarray having immobilized thereon a plurality of probes, wherein at least one of said probes is specific for an isolated nucleic acid molecule comprising all or a portion of at least 10 contiguous nucleotides of the PPARα nucleotide sequence, as exemplified by SEQ ID NO: 1, or an allelic varient thereof, wherein the isolated nucleic acid molecule comprises a polymorphic site at nucleotide position 696 of the PPARα gene which is occupied by a guanine (G), and wherein said probe comprises the polymorphic site.  
     
     
         9 . An isolated nucleic acid molecule comprising all or a portion of at least 10 contiguous nucleotides of the PPARα nucleotide sequence, as exemplified by SEQ ID NO: 1, or an allelic varient thereof, wherein the isolated nucleic acid molecule comprises a polymorphic site at nucleotide position 971 of the PPARα gene which is occupied by an adenine (A), and complements of said isolated nucleic acid molecule.  
     
     
         10 . An expression vector comprising the isolated nucleic acid molecule of  claim 9 .  
     
     
         11 . A host cell comprising the expression vector of  claim 10 .  
     
     
         12 . A nucleic acid molecule which specifically hybridizes under conditions of high stringency to an isolated nucleic acid molecule comprising all or a portion of at least 10 contiguous nucleotides of the PPARα nucleotide sequence, as exemplified by SEQ ID NO: 1, or an alletic varient thereof, wherein the isolated nucleic acid molecule comprises a polymorphic site at nucleotide position 971 of the PPARα gene which is occupied by an adenine (A) and wherein said nucleic acid molecule comprises the polymorphic site.  
     
     
         13 . A nucleic acid molecule which has at least 90% sequence identity with an isolated nucleic acid molecule comprising all or a portion of at least 10 contiguous nucleotides of the PPARα nucleotide sequence, as exemplified by SEQ ID NO: 1, or an allelic varient thereof, wherein the isolated nucleic acid molecule comprises a polymorphic site at nucleotide position 971 of the PPARα gene which is occupied by an adenine (A) and wherein said nucleic acid molecule comprises the polymorphic site.  
     
     
         14 . An oligonucleotide microarray having immobilized thereon a plurality of probes, wherein at least one of said probes is specific for an isolated nucleic acid molecule comprising all or a portion of at least 10 contiguous nucleotides of the PPARA nucleotide sequence, as exemplified by SEQ ID NO: 1, or an allelic varient thereof, wherein the isolated nucleic acid molecule comprises a polymorphic site at nucleotide position 971 of the PPARα gene which is occupied by an adenine (A) and wherein said probe comprises the polymorphic site.  
     
     
         15 . An isolated nucleic acid molecule comprising all or a portion of at least 275 contiguous nucleotides of the PPARα nucleotide sequence, as exemplified by SEQ ID NO: 1, or an allelic varient thereof, wherein the isolated nucleic acid molecule comprises a polymorphic site at nucleotide position 696 of the PPARα gene and a polymorphic site at nucleotide position 971 of the PPARα gene which are occupied by a guanine (G) and an adenine (A), respectively, and complements of said isolated nucleic acid molecule.  
     
     
         16 . An expression vector comprising the isolated nucleic acid molecule of  claim 15 .  
     
     
         17 . A host cell comprising the expression vector of  claim 16 .  
     
     
         18 . An oligonucleotide microarray having immobilized thereon a plurality of probes, wherein at least one of said probes is specific for the isolated nucleic acid molecule comprising all or a portion of at least 275 contiguous nucleotides of the PPARα nucleotide sequence, as exemplified by SEQ ID NO: 1, or an allelic varient thereof, wherein the isolated nucleic acid molecule comprises a polymorphic site at nucleotide position at nucleotide position 696 of the PPARα gene and a polymorphic site at nucleotide position 971 of the PPARα gene which is occupied by a guanine (G) and an adenine (A), respectively, and wherein said probe comprises the polymorphic sites.