Methods and compositions for detecting and treating genetically induced chronic diseases

An isolated polynucleotide probe for detecting an ATTG D allele polymorphism of a human NFKB1 promoter, wherein said probe specifically binds to the ATTG D allele but exhibits little or no binding to the ATTG W allele of the NFKB1 promoter.

An isolated polynucleotide probe for detecting an ATTG W polymorphism in a mammalian NFKB1 promoter, wherein said probe specifically binds to the ATTG W allele of said promoter but exhibits little or no binding to the ATTG D allele of the NFKB1 promoter.

A method for identifying an individual at increased risk for developing a pathogenic condition, comprising determining the presence of a functional polymorphism in the NFKB1 gene promoter of said individual, wherein the polymorphism is indicative of an increased risk to develop the pathogenic condition.

A method for identifying an individual at increased risk for developing an inflammatory bowel disease, comprising determining presence of a −94del ATTG allele in the NFKB1 gene promoter of said individual wherein the ATTG polymorphism is indicative of an increased risk to develop inflammatory bowel disease compared with an individual having a −94insATTG allele.

A mammalian NFKB1 promoter binding protein that selectively binds to NFKB1 −94insATTG duplet promoter but exhibits little or no binding to the NFKB1-94delATTG singlet allele or to other NFKB1 binding sites.

The NFKB1 promoter binding protein identified as NFKB1-PIP

A kit for detecting a −94ins/del ATTG polymorphism in a NFKB1 promoter, said kit comprising at least one oligonucleotide probe that selectively hybridizes to a −94delATTG, optionally at least one oligonucleotide probe that selectively hybridizes to a −94insATTG polymorphism, and directions for use.

27A. The kit of claim 25 wherein the oligonucleotide probe for detecting the −94insATTG polymorphism is a probe having the sequence of SEQ ID NO:5.

A method of determining risk or presence of an inflammatory disease in an individual, comprising determining binding of mammalian nuclear proteins to a functional polymorphism sequence in an NFKB1 promoter gene wherein the functional polymorphism sequence is C/C or C/G at exon 1+252 of NFKB1 and wherein said nuclear proteins exhibit decreased binding compared with binding to corresponding wildtype allele of NFKB1.

A method of determining risk or presence of inflammatory bowel disease in an individual, comprising determining binding of mammalian nuclear protein NFKB1-PIP to the −94delATTG allele in NFKB1 promoter, wherein decreased binding of the NFKB1-PIP compared with wildtype −94ins/delATTG polymorphism is indicative of inflammatory bowel disease.

A method for determining the presence of a −94del ATTG polymorphism in an individual homozygous or heterozygous for the polymorphism, comprising amplifying genomic DNA with 5′ to 3′ forward and reverse primers designed to bracket positions −91 to −94 in SEQ ID NO:1, cleaving the product by enzyme digestion and identifying the −94 del ATTG polymorphism by selective hybridization with a detectable oligonucleotide probe.

An isolated human NFKB1 promoter gene comprising a nucleic acid sequence that selectively binds to SEQ ID NO:4.

An isolated oligonucleotide comprising a contiguous nucleotide sequence of human NKFB1 promoter comprising an ATTG singlet as a polymorphism −94ins/delATTG of SEQ ID NO:1 wherein said sequence maintains NKFB1 promoter function.

A method of treating an individual having symptoms of inflammatory bowel disease, comprising administering to said individual a pharmaceutically effective composition that promotes increased binding of nuclear proteins to NKFB1 promoter, wherein the increased binding is comparable to binding of nuclear proteins to wildtype NKFB1 promoter.

A pharmaceutical composition effective to enhance or promote binding of nuclear proteins to a NKFB1 promoter having an ATTG deletion, said composition comprising a nuclear binding polypeptide modified to bind at about 15-20 bp 5′ or 3′ of position −94 of SEQ ID NO:1.