Methods of predicting predisposition to or risk of kidney disease

Abstract

Methods are disclosed herein for detecting a genetic predisposition to focal segmental glomerulosclerosis (FSGS) or hypertensive end-stage kidney disease (ESKD) or both in a human subject. The methods include detecting the presence of at least one single nucleotide polymorphism (SNP) in an APOL1 gene, such as the C-terminal exon of an APOL1 gene. In a further embodiment, methods are disclosed for detecting resistance of a subject to a disease associated with Trypanosoma infection. The methods include detecting the presence of at least one single nucleotide polymorphism (SNP) in an APOL1 gene, such as the C-terminal exon of an APOL1 gene. Also disclosed are methods for treating a subject infected with T brucei (such as T. brucei brucei, T b. rhodesiense, or T b. gambiense). The methods include administering a therapeutically effective amount of an APOL1 protein including a S342G substitution, an I384M substitution, and/or a deletion of N388 and Y389 to the subject.

1 - 88 . (canceled) 
     
     
         89 . A method for selecting a human subject for treatment to reduce the risk of developing renal failure or delay the development of renal failure, the method comprising:
 determining the presence of at least one apolipoprotein L1 (APOL1) gene risk allele in the subject.   
     
     
         90 . The method of  claim 89 , wherein the at least one human APOL1 gene risk allele comprises at least one single nucleotide polymorphism (SNP) and/or at least one inversion in a human APOL1 gene. 
     
     
         91 . The method of  claim 90 , wherein the at least one SNP produces an APOL1 polypeptide having a serine to glycine mutation at position 342 (S342G), an isoleucine to methionine mutation at position 384 (I384M), a deletion of amino acids N388 and Y389, or a combination thereof. 
     
     
         92 . The method of  claim 91 , wherein the at least one SNP produces an APOL1 polypeptide having a S342G and an I384M mutation. 
     
     
         93 . The method of  claim 90 , wherein the method comprises determining the presence of the at least one SNP and/or the at least one inversion on both chromosomes of the subject. 
     
     
         94 . The method of  claim 89 , wherein the renal disease is focal segmental glomerulosclerosis (FSGS) or hypertensive end-stage kidney disease, or both. 
     
     
         95 . The method of  claim 89 , wherein the subject is of African or Hispanic ancestry. 
     
     
         96 . The method of  claim 90 , comprising determining the presence of the at least SNP and the at least one inversion in the human APOL1 gene. 
     
     
         97 . The method of  claim 90 , wherein the inversion comprises recombination between said human APOL1 gene and a human apolipoprotein 4 (APOL4) gene or the inversion comprises substitution of the 5′ region of said APOL1 gene with the 5′ region of an APOL4 gene 
     
     
         98 . The method of  claim 90 , wherein said inversion occurs in a coding region of said APOL1 gene, a non-coding region of said APOL1 gene, or in both regions. 
     
     
         99 . The method of  claim 89 , wherein the nucleic acid molecule having the sequence of at least one APOL1 gene risk allele or a complement thereof has a nucleotide sequence of SEQ ID NO:1, SEQ ID NO:2 and/or SEQ ID NO:3 or a complement thereof, or the nucleic acid primer capable of amplifying the nucleic acid molecule or complement thereof has a nucleotide sequence of SEQ ID NO:1, SEQ ID NO:2 and/or SEQ ID NO:3. 
     
     
         100 . The method of  claim 99 , wherein the determining further comprises determining the presence or absence of a G allele at single nucleotide polymorphism (SNP) rs73885319 in the nucleotide sequence of SEQ ID NO:1, the presence or absence of a G allele at SNP rs60910145 in the nucleotide sequence of SEQ ID NO:2, and the presence or absence of a six base pair deletion at SNP rs71785313 in the nucleotide sequence of SEQ ID NO:3. 
     
     
         101 . The method of  claim 89 , wherein the biological sample is selected from the group consisting or whole blood, serum, buccal cells, extracted galls, biopsied or surgically removed tissue, tears, milk, a skin scrape, a surface washing, urine, sputum, cerebrospinal fluid, prostate fluid, pus, and a bone marrow aspirate. 
     
     
         102 . The method of  claim 89 , wherein testing the subject for the presence of at least one APOL1 gene risk allele comprises:
 i) contacting a biological sample from the human subject with a nucleic acid probe capable of hybridizing to a nucleic acid molecule having the sequence of at least one apolipoprotein L1 (APOL1) gene risk allele or a complement thereof, or a nucleic acid primer capable of amplifying the nucleic acid molecule or complement thereof;   ii) detecting formation of a hybridization complex between the nucleic acid probe and the nucleic acid molecule or complement thereof or an amplification product corresponding to the nucleic acid molecule or complement thereof; and   iii) selecting the human subject for treatment to reduce the risk of developing renal failure renal failure or delay the development of renal failure in which the formation of a hybridization complex or an amplification product is detected.   
     
     
         103 . A method for selecting a human subject in need of screening for renal disease and/or for the risk of developing renal disease, the method comprising:
 determining the presence of an apolipoprotein L1 (APOL1) gene risk allele in a biological sample of the subject; and   selecting the subject in which the APOL1 gene risk allele is present in the biological sample for screening for renal disease and/or for the risk of developing renal injury/disease.   
     
     
         104 . The method of  claim 103 , wherein the screening of the subject is an annual or biannual screening for renal disease and/or for risk of developing renal injury/disease. 
     
     
         105 . The method of  claim 103 , wherein the APOL1 gene risk allele comprises at least one SNP and/or at least one inversion in a human APOL1 gene. 
     
     
         106 . The method of  claim 105 , wherein the at least one SNP produces an APOL1 polypeptide having a serine to glycine mutation at position 342 (S342G), an isoleucine to methionine mutation at position 384 (I384M), a deletion of amino acids N388 and Y389, or a combination thereof. 
     
     
         107 . The method of  claim 106 , wherein the at least one SNP produces an APOL1 polypeptide having a S342G and an I384M mutation. 
     
     
         108 . The method of  claim 105 , wherein the method comprises determining the presence of the at least one SNP and/or the at least one inversion on both chromosomes of the subject. 
     
     
         109 . The method of  claim 103 , wherein the renal disease is focal segmental glomerulosclerosis (FSGS) or hypertensive end-stage kidney disease, or both. 
     
     
         110 . The method of  claim 103 , wherein the subject is of African or Hispanic ancestry. 
     
     
         111 . The method of  claim 105 , comprising determining the presence of the at least SNP and the at least one inversion in the human APOL1 gene. 
     
     
         112 . The method of  claim 105 , wherein the inversion occurs in a coding region of said APOL1 gene, a non-coding region of said APOL1 gene, or in both regions. 
     
     
         113 . The method of  claim 105 , wherein the inversion comprises recombination between said human APOL1 gene and a human apolipoprotein 4 (APOL4) gene or the inversion comprises substitution of the 5′ region of said APOL1 gene with the 5′ region of an APOL4 gene. 
     
     
         114 . The method of  claim 103 , wherein the at least one APOL1 gene risk allele comprises a nucleotide sequence of SEQ ID NO:1, SEQ ID NO:2 and/or SEQ ID NO:3 or a complement thereof. 
     
     
         115 . The method of  claim 114 , wherein the determining further comprises determining the presence or absence of a G allele at single nucleotide polymorphism (SNP) rs73885319 in the nucleotide sequence of SEQ ID NO:1, the presence or absence of a G allele at SNP rs60910145 in the nucleotide sequence of SEQ ID NO:2, and the presence or absence of a six base pair deletion at SNP rs71785313 in the nucleotide sequence of SEQ ID NO:3. 
     
     
         116 . The method of  claim 103 , wherein the determining further comprises
 a) contacting the biological sample from the human subject with a nucleic acid probe capable of hybridizing to a nucleic acid molecule having the sequence of at least one apolipoprotein L1 (APOL1) gene risk allele or a complement thereof, or a nucleic acid primer capable of amplifying the nucleic acid molecule or complement thereof;   b) determining formation of a hybridization complex between the nucleic acid probe and the nucleic acid molecule or complement thereof or an amplification product corresponding to the nucleic acid molecule or complement thereof; and   c) selecting the human subject for screening for renal disease and/or risk of developing renal disease in which the formation of a hybridization complex or an amplification product is detected.   
     
     
         117 . The method of  claim 116 , wherein the nucleic acid molecule having the sequence of at least one APOL1 gene risk allele or a complement thereof has a nucleotide sequence of SEQ ID NO:1, SEQ ID NO:2 and/or SEQ ID NO:3 or a complement thereof, or the nucleic acid primer capable of amplifying the nucleic acid molecule or complement thereof has a nucleotide sequence of SEQ ID NO:1, SEQ ID NO:2 and/or SEQ ID NO:3. 
     
     
         118 . The method of  claim 117 , wherein the determining further comprises determining the presence or absence of a G allele at single nucleotide polymorphism (SNP) rs73885319 in the nucleotide sequence of SEQ ID NO:1, the presence or absence of a G allele at SNP rs60910145 in the nucleotide sequence of SEQ ID NO:2, and the presence or absence of a six base pair deletion at SNP rs71785313 in the nucleotide sequence of SEQ ID NO:3 
     
     
         119 . The method of  claim 103 , wherein the biological sample is selected from the group consisting or whole blood, serum, buccal cells, extracted galls, biopsied or surgically removed tissue, tears, milk, a skin scrape, a surface washing, urine, sputum, cerebrospinal fluid, prostate fluid, pus, and a bone marrow aspirate.