Cedars-sinai Medical Center

University of California

Cedars-sinai Medical

Huiying Yang

Jerome I Rotter

Stephan R Targan

Kent D Taylor

Scott E Plevy

Arthur L Beaudet

Eric A Vasiliauskas

Devendra Vora

Phillip R Fleshner

Xiuqing Guo

Hiroo Toyoda

William S Mow

Mark O Goodarzi

Leslie J Raffel

Willa A Hsueh

Stephen R Targan

Maren Theresa Scheuner

Yii-Der Ida Chen

Maria T Abreu

Theresa Pizarro

Fabio Cominelli

Maren Scheuner

Kazuhito Sugimura

Disclosed is a method for determining haplotypes useful for large-scale genetic analysis, within a genomic reference sequence of interest, for a human subpopulation. The method can applied to statistically evaluating the genotypes of subjects for any statistically significant association with a phenotype of interest, such as insulin resistance or coronary artery disease. Thus, also disclosed are a method of detecting a genetic predisposition in a human subject for certain biological conditions, which may be related to coronary artery disease.

Method of haplotype-based genetic analysis for determining risk for developing insulin resistance, coronary artery disease and other phenotypes

The invention provides a method of diagnosing or predicting susceptibility to a clinical subtype of Crohn's disease in a subject having Crohn's disease by determining the presence or absence of IgA anti-I2 antibodies in the subject, where the presence of the IgA anti-I2 antibodies indicates that the subject has a clinical subtype of Crohn's disease. In one embodiment, a method of the invention is practiced by further determining the presence or absence in the subject of a NOD2 variant, anti-antibodies (ASCA), IgA anti-OmpC antibodies, or perinuclear anti-neutrophil cytoplasmic antibodies (pANCA). The methods of the invention can be used to diagnose or predict susceptibility to a clinical subtype of Crohn's disease, for example, a fibrostenotic subtype, a subtype characterized by the need for small bowel surgery, or a subtype characterized by the absence of features of ulcerative colitis.

Methods of assessing Crohn's disease patient phenotype by I2 serologic response

The present invention provides a method of diagnosing or predicting susceptibility to a clinical subtype of Crohn's disease characterized by fibrostenosing disease by determining the presence or absence in an individual of a fibrostenosis-predisposing allele linked to a NOD2/CARD15 locus, where the presence of the fibrostenosis-predisposing allele is diagnostic of or predictive of susceptibility to the clinical subtype of Crohn's disease characterized by fibrostenosing disease. In a method of the invention, the clinical subtype of Crohn's disease can be, for example, characterized by fibrostenosing disease independent of small bowel involvement. The invention also provides a method of optimizing therapy in an individual by determining the presence or absence in the individual of a fibrostenosis-predisposing allele linked to a NOD2/CARD15 locus, diagnosing individuals in which the fibrostenosis-predisposing allele is present as having a fibrostenosing subtype of Crohn's disease, and treating the individual having a fibrostenosing subtype of Crohn's disease based on the diagnosis.

Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease

The present invention provides a method of diagnosing or predicting susceptibility to an autoimmune disease in an individual by determining the presence or absence in the individual of a 2-2-4 haplotype at the Notch4, HSP70-HOM and D6S273 loci, where the presence of the haplotype diagnoses or predicts susceptibility to the autoimmune disease. The methods of the invention can be particularly useful for diagnosing or predicting susceptibility to Crohn's disease, rheumatoid arthritis or type I diabetes mellitus. In a preferred embodiment, a method of the invention is used to diagnose or predict susceptibility to Crohn's disease in an individual of Ashkenazi Jewish ethnicity.

Methods of using a major histocompatibility complex class III haplotype to diagnose Crohn's disease

Disclosed is a method for determining haplotypes useful for large-scale genetic analysis, within a genomic reference sequence of interest, for a human subpopulation. The method can applied to statistically evaluating the genotypes of subjects for any statistically significant association with a phenotype of interest, such as insulin resistance or coronary artery disease. Thus, also disclosed are a method of detecting a genetic predisposition in a Mexican-American human subject for developing insulin resistance and methods of detecting a lower than normal risk in a Mexican-American human subject for developing insulin resistance or coronary artery disease.

Method of haplotype-based genetic analysis for determining risk for developing insulin resistance and coronary artery disease

A novel association between IBD and a polymorphism at amino acid residue 241 of ICAM-1 has been discovered. In accordance with the present invention there is provided methods of screening for IBD, methods for treating IBD, antibodies specifically reactive with ICAM-1 encoded by, R241 allele and kits which exploit the inventive methods.

Methods of screening for ulcerative colitis and crohn's disease

A novel association between certain tumor necrosis factor microsatellite alleles and Crohn's disease has been discovered. In accordance with the present invention, there is provided methods for screening for Crohn's disease comprising detecting the presence or absence of nucleic acid of a subject encoding TNF microsatellite alleles associated with Crohn's disease, wherein the presence of nucleic acid encoding three or more of the alleles is indicative of Crohn's disease. Kits useful for screening for Crohn's disease are also provided which comprise nucleic acid encoding TNF microsatellite alleles associated with Crohn's disease.

Methods of screening for Crohn's disease using TNF microsatellite alleles

In a method for detecting a genetic predisposition in a human for non-responsiveness to statin drug treatment for coronary artery disease, nucleic acids comprising nucleotide sequences of the human lipoprotein lipase (LPL) gene are amplified and analyzed. Homozygosity for a variant allele in a non-coding or untranslated region of the 3&prime; end of LPL, for example, LPL HindIII 2/2 or (TTTA),4/4 genotypes, is linked to non-responsiveness to treatment with statin drugs, including lovastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, or cerivastatin. Oligonucleotide primer sequences, primer sets, and genetic testing kits allow the practitioner to practice the method and thus better individualize the treatment and improve the care of patients with coronary artery disease.

Genetic test to determine non-responsiveness to statin drug treatment

A novel association between IBD and a polymorphism at amino acid residue 241 of ICAM-1 has been discovered. In accordance with the present invention there is provided methods of screening for IBD, methods for treating IBD, antibodies specifically reactive with ICAM-1 encoded by R241 allele and kits which exploit the inventive methods.

Methods of screening for ulcerative colitis and Crohn's disease

A novel, differential association between allele 2 of the variable number of tandem repeats polymorphism at intron 2 of the human IL-1 receptor antagonist gene and ulcerative colitis in humans of Jewish ancestry has been discovered. In accordance with the present invention, there is provided methods of screening for ulcerative colitis in human subjects of Jewish ancestry comprising detecting the presence or absence of nucleic acid of the subject encoding allele 2 of the variable number of tandem repeats polymorphism at intron 2 of the human IL-1 receptor antagonist gene, wherein the presence of nucleic acid encoding allele 2 is indicative of ulcerative colitis. Kits useful for screening for ulcerative colitis in human subjects of Jewish ancestry are also provided.

Method of diagnosing predisposition for ulcerative colitis in Jewish

The present invention provides a method of diagnosing a clinical subtype of Crohn's disease (CD) by determining whether perinuclear anti-neutrophil antibodies (pANCA) are present in a patient with CD, where the presence of pANCA indicates the clinical subtype of CD with features of ulcerative colitis (UC). The invention also provides a method of diagnosing a clinical subtype of CD by detecting an Arg.sup.241 allele at an ICAM-1 locus in a patient with CD, where the Arg.sup.241 allele indicates a clinical subtype of CD with features of ulcerative colitis. In addition, the invention provides a method of diagnosing a pANCA-positive subtype of CD by detecting an Arg.sup.241 allele at an ICAM-1 locus in a patient with CD, where the Arg.sup.241 allele indicates the pANCA-positive subtype of CD.

Method of diagnosing a clinical subtype of crohn's disease with features

A novel association between IBD and a polymorphism at amino acid residue 241 of ICAM-1 has been discovered. In accordance with the present invention there is provided methods of screening for IBD, methods for treating IBD, antibodies specifically reactive wish ICAM-1 encoded by R241 allele and kits which exploit the inventive methods.

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Cerritos, CA, United States of America

Huiying Yang