US 12,620,489 B2Granted

Method for determining the risk to develop type 1 diabetes

AssigneesHelmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Technische UniversitäT Dresden

InventorsAnette-G. Ziegler, Ezio Bonifacio, Christiane Winkler, Jan Krumsiek, Fabian Theis, Peter Achenbach

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Abstract

The present invention relates to a method of determining whether a subject is at risk of developing type 1 diabetes by determining the genetic risk score (GRS) of a subject. The present invention also comprises a pharmaceutical composition comprising insulin and a pharmaceutical acceptable carrier for use in a method for preventing type 1 diabetes in a subject having a genetic risk score as determined by the method mentioned above. Further, it encompasses a kit for use in a method of determining whether a subject is at risk of developing type 1 diabetes by determining the genetic risk score of a subject and a type 1 diabetes antigen for use in a method of immunizing a subject against type 1 diabetes having a genetic risk score as determined by the method mentioned above.

Claims7

Dependent claims

A kit for determining a genetic risk score for developing type 1 diabetes, comprising:

an oligonucleotide comprising SEQ ID NO:
1;
an oligonucleotide comprising SEQ ID NO:
2;
an oligonucleotide comprising SEQ ID NO:
3;
an oligonucleotide comprising SEQ ID NO:
4;
an oligonucleotide comprising SEQ ID NO:
5;
an oligonucleotide comprising SEQ ID NO:
6;
an oligonucleotide comprising SEQ ID NO:
7;
an oligonucleotide comprising SEQ ID NO:
8;
an oligonucleotide comprising SEQ ID NO:
9;
an oligonucleotide comprising SEQ ID NO:
10;
an oligonucleotide comprising SEQ ID NO:
11;
an oligonucleotide comprising SEQ ID NO:
12;
an oligonucleotide comprising SEQ ID NO:
13;
an oligonucleotide comprising SEQ ID NO:
14;
an oligonucleotide comprising SEQ ID NO:
15;
an oligonucleotide comprising SEQ ID NO:
16;
an oligonucleotide comprising SEQ ID NO:
17;
an oligonucleotide comprising SEQ ID NO:
18;
an oligonucleotide comprising SEQ ID NO:
19;
an oligonucleotide comprising SEQ ID NO:
20;
an oligonucleotide comprising SEQ ID NO:
21;
an oligonucleotide comprising SEQ ID NO:
22;
an oligonucleotide comprising SEQ ID NO:
23;
an oligonucleotide comprising SEQ ID NO:
24;
an oligonucleotide comprising SEQ ID NO:
25;
an oligonucleotide comprising SEQ ID NO:
26;
an oligonucleotide comprising SEQ ID NO:
27;
an oligonucleotide comprising SEQ ID NO:
28;
an oligonucleotide comprising SEQ ID NO:
29;
an oligonucleotide comprising SEQ ID NO:
30;
an oligonucleotide comprising SEQ ID NO:
31;
an oligonucleotide comprising SEQ ID NO:
32;
an oligonucleotide comprising SEQ ID NO:
33;
an oligonucleotide comprising SEQ ID NO:
34;
an oligonucleotide comprising SEQ ID NO:
35;
an oligonucleotide comprising SEQ ID NO:
36;
an oligonucleotide comprising SEQ ID NO:
37;
an oligonucleotide comprising SEQ ID NO:
38;
an oligonucleotide comprising SEQ ID NO:
39;
an oligonucleotide comprising SEQ ID NO:
40;
an oligonucleotide comprising SEQ ID NO:
41;
and
an oligonucleotide comprising SEQ ID NO:
42.

82 more elements

A method of immunizing a subject against type 1 diabetes, comprising administering to the subject a type 1 diabetes antigen, wherein the subject is determined to be at risk of developing type 1 diabetes by a method of:

(a) multiplying the corresponding score weight per risk allele of each of the 41 single nucleotide polymorphisms (SNPs), listed in the table below, with the corresponding number of risk alleles determined in a sample from the subject for each of the 41 SNPs,
SNP
score weight per allele
rs1264813
0.43
rs2395029
0.92
rs2476601
0.76
rs2816316
0.16
rs3024505
0.22
rs1990760
0.16
rs3087243
0.16
rs10517086
0.19
rs2069763
0.11
rs6897932
0.19
rs3757247
0.19
rs9388489
0.14
rs6920220
0.15
rs1738074
0.05
rs7804356
0.15
rs4948088
0.17
rs7020673
0.23
rs12722495
0.47
rs947474
0.15
rs10509540
0.25
rs689 or rs1004446
0.65
rs4763879
0.06
rs2292239
0.36
rs3184504
0.24
rs1465788
0.13
rs17574546
0.13
rs3825932
0.15
rs12708716
0.15
rs4788084
0.20
rs7202877
0.19
rs2290400
0.25
rs7221109
0.15
rs45450798
0.09
rs763361
0.12
rs425105
0.21
rs2281808
0.07
rs3788013
0.16
rs5753037
0.15
rs229541
0.18
rs5979785
0.09
rs2664170
0.14
wherein the number of risk alleles for each SNP is 0 if a risk allele of the SNP is determined to be not present, 1 if a risk allele of the SNP is determined to be present heterozygously, or 2 if a risk allele of the SNP is determined to be present homozygously;
(b) assigning a score number of 3.15 if SNP rs17426593, SNP rs2187668, and SNP rs7454108 are determined in the subject having a HLA DR4-DQ8/DR4-DQ8 genotype and a score number of 3.98 if SNP rs17426593, SNP rs2187668, and SNP rs7454108 are determined in the subject having a HLA DR3/DR4-DQ8 genotype;
and
(c) summing up multiplication products of step (a) and any corresponding assigned score number of step (b) determined in the subject, thereby obtaining a genetic risk score, wherein the genetic risk score equal to or greater than 13.47 is indicative that the subject is at risk of developing type 1 diabetes,
wherein said type 1 diabetes antigen is administered to the subject at a dose of 50 to 100 mg, wherein said type 1 diabetes antigen is administered orally and daily, and wherein said type 1 diabetes antigen is selected from the group consisting of insulin, proinsulin, insulin analog, and peptides thereof, thereby immunizing a subject against type 1 diabetes.

87 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/626,200Filed 27 Jun 2018
Priority: EP 1717839628 Jun 2017
Published: US 2020/0126671 A123 Apr 2020
Granted: 5 May 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification17 codes

G16H 50/30
ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or…: for…
C12Q 1/6883
Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes: for diseases caused by alterations of genetic material
G01N 33/49
Of liquid biological material: blood
G16B 20/20
ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations: allele or variant detection, e.g. single…