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1. WO2006099142 - PROGNOSTIC METHOD FOR VASCULAR DISEASES

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CLAIMS
We claim:
1. A method of predicting vascular disease in an individual, wherein the method comprises the steps of genotyping a biological sample from an individual for at least one polymorphism per gene locus, where the gene loci comprise at least 3 genes selected from the group consisting of ADCY9 (NM _001116); ANXA2 (NM_001002858); BMP6
(NM_001718); CCL2 (NM_002982); CSF2 (NM_000758); ECEl (NM_001397 or its transcription variant NM_182918); ERG (NM_004449); MET (NM_000245); SELP
(NM_003005); TEK (NM_000459); and TGFBR3 (NM_003243), wherein when 5 or fewer genes are selected, at least SELP or BMP6 are included into the group of analyzed loci, and wherein the risk of vascular disease is increased when the individual carries at least one allele of a group of two alleles that is different from the allele that cosegregates within a control population associated with low risk for vascular disease.

2. The method of claim 1 , wherein the at least one allele is present in a genotype selected from the group consisting of genotype GG or AA in the polymorphic marker hCV26910500 or any marker in tight linkage disequilibrium with these alleles in or around ANXA2 gene locus; a genotype TT in the polymorphic marker rs267196 or any marker in tight linkage disequilibrium with these alleles in or around BMP6 gene locus; a genotype CC in the polymorphic marker rs408505 or any marker in tight linkage disequilibrium with these alleles in or around BMP6 gene locus; a genotype CT or CT in the polymorphic marker rs3917733 rs408505 or any marker in tight linkage disequilibrium with these alleles in or around SELP gene locus; a genotype CC in the polymorphic marker rs284875 or any marker in tight linkage disequilibrium with these alleles in or around TGFRBR3 gene locus; and/or a genotype AA in the polymorphic marker rs989554 or any marker in tight linkage
disequilibrium with these alleles in or around ERG gene locus.

3. The method of claim 1 or 2, wherein the cerebrovascular disease is a stroke.

4. The method of claims 1, 2, or 3, wherein the individual has sickle cell anemia.

5. The method of claim 1 or 2, wherein the polymorphic markers comprise at least 5-11 markers selected from the group consisting of rs437115, rs2238432, rs2238426, rs2072338, rs2283497, hCV26910500, rs267196, rs267201, rs408505, rs449853, rs4586, rs25882, rs212528, rs212531, rs989554, rs38850, rs38859, rs2420378, rs3917733, rs3753306, rs489347, rs284875, rs2148322, rs2765888, and rs2007686.

6. A method of selecting an individual for close medical follow-up and/or prophylactic treatment for stroke comprising the steps of genotyping a biological sample from an individual for at least one polymorphism per gene locus, where the gene loci comprise at least 3 genes selected from the group consisting of ADCY9 (NMJ)Ol 116); ANXA2
(NM__001002858); BMP6 (NM_001718); CCL2 (NM_002982); CSF2 (NM_000758); ECEl (NM_001397 or its transcription variant NM_182918); ERG (NM_004449); MET
(NM_000245); SELP (NM_OO3005); TEK (NM_000459); and TGFBR3 (NM_003243), wherein when 5 or fewer genes are selected, at least SELP or BMP6 are included into the group of analyzed loci, and wherein the individual is selected for for close medical follow-up and/or prophylactic treatment of stroke if the individual carries at least one allele of a group of two alleles that is different from the allele that cosegregates within a control population associated with low risk for stroke.

7. The method of claim 6, wherein at least one of the alleles is present in a genotype selected from the group consisting of genotype GG or AA in the polymorphic marker hCV26910500 or any marker in tight linkage disequilibrium with these alleles in or around ANXA2 gene locus; a genotype TT in the polymorphic marker rs267196 or any marker in tight linkage disequilibrium with these alleles in or around BMP6 gene locus; a genotype CC in the polymorphic marker rs408505 or any marker in tight linkage disequilibrium with these alleles in or around BMP6 gene locus; a genotype CT or CT in the polymorphic marker rs3917733 rs408505 or any marker in tight linkage disequilibrium with these alleles in or around SELP gene locus; a genotype CC in the polymorphic marker rs284875 or any marker in tight linkage disequilibrium with these alleles in or around TGFRBR3 gene locus; and/or a genotype AA in the polymorphic marker rs989554 or any marker in tight linkage
disequilibrium with these alleles in or around ERG gene locus.

8. The method of claims 5 or 6, wherein the individual has sickle cell anemia.

9. A kit for selecting an individual with sickle cell anemia for a close medical follow-up group for development of stroke comprising primers for amplifying the nucleic acid sample from an individual, and a system for genotyping the individual for polymorphisms in a group of genes comprising at least three of the genes selected from the group consisting of ANXA2 (hCV26910500); BMP6 (rs267196 and rs408505); ERG (rs989554); SELP (rs3917733); and TGFBR3 (rs284875), and an instruction booklet wherein high and low risk genotypes are indicated in a Table 3 form and instructions on the individuals based on the genotype combinations that need to be closely followed or prophylactically treated for stroke.