Az 1-es típusú diabetes és a prediktív genetikai szurés lehetoségei a magyar populációban

Translated title of the contribution: Predictive genetic screening for type 1 diabetes in the Hungarian population

Róbert Hermann, G. Soltész

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Introduction: In the modern genetic era the principles of genetic screening are being changed. In addition to diagnostic screening for rare monogenic diseases, predictive screening for common polygenic conditions, like type 1 diabetes, will be more widely implemented. The majority of the genetic background of type 1 diabetes is encoded by the HLA DQ and DR genes, selected variants of which could be used as screening markers. However, risk conferred by various HLA genotypes shows considerable ethnic variation, therefore population-specific screening markers need to be established. Aims: The aim of this study was to describe a screening strategy based on risk-defining HLA DRB1-DQA1-DQB1 markers to identify individuals at risk for type 1 diabetes in the Hungarian population. Methods: HLA genotypes of 149 consecutively diagnosed children with type 1 diabetes (age at diagnosis 0-14, mean 8.8 ± 4.2 years) and 177 randomly selected healthy schoolchildren were studied. Allele-specific polymerase chain reaction method was used for HLA typing. The diagnostic sensitivity, specificity and predictive value of diabetes associated DRB1-DQA1-DQB1 alleles were analysed in a step-wise strategy. Results: The highest diagnostic sensitivity was detected when DQB1 typing was complemented by DQA1 typing on DQB1*0201 positive samples with additional DRB1*04 subtyping in DQB1*0302 carriers. The combination of the following markers gave a relative risk of 28.9 (95% confidence interval: 15.9-52.7, p = 10 -6): DQB1*0201/0302-DQA1*0301,0501-b (b ≠ DRB1* 0403), DQB1*0302/x-DRB1*0401,0402 (≠ DQB1*0201, 0301,0602,0603), DQB1*0301/0302-DRB1*0401,0404, DQB1*0304/s (s = any DQB1 alleles), DQB1*0201/y-DQA1*0501/a (y ≠ DQB1*0301,0302,0602, 0603,0604, a ≠ DQA1*0201). The diagnostic sensitivity, specificity and positive predictive values for this marker combination were 79.2%, 88.7%, and 1.1%, respectively. Conclusions: Using HLA DRB1-DQA1-DQB1 markers predictive genetic screening for type 1 diabetes is feasible in the Hungarian population with high diagnostic sensitivity and specificity. At present, such a screening for individuals at risk for type 1 diabetes in the general population is recommended only as part of prospective studies on the natural history or prevention of disease. To increase the positive predictive value of the model, pancreas β-cell autoantibodies need to be measured and followed in the high-risk cohort.

Original languageHungarian
Pages (from-to)337-342
Number of pages6
JournalOrvosi Hetilap
Volume145
Issue number7
Publication statusPublished - Feb 2004

Fingerprint

Genetic Testing
Type 1 Diabetes Mellitus
Population
HLA-DRB1 Chains
Alleles
Sensitivity and Specificity
Genotype
HLA-DQ Antigens
Histocompatibility Testing
HLA-DR Antigens
Rare Diseases
Natural History
Autoantibodies
Pancreas
Prospective Studies
Confidence Intervals
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Az 1-es típusú diabetes és a prediktív genetikai szurés lehetoségei a magyar populációban. / Hermann, Róbert; Soltész, G.

In: Orvosi Hetilap, Vol. 145, No. 7, 02.2004, p. 337-342.

Research output: Contribution to journalArticle

@article{d57589a38dbe49d2b35a1ea9ffeae2a9,
title = "Az 1-es t{\'i}pus{\'u} diabetes {\'e}s a predikt{\'i}v genetikai szur{\'e}s lehetos{\'e}gei a magyar popul{\'a}ci{\'o}ban",
abstract = "Introduction: In the modern genetic era the principles of genetic screening are being changed. In addition to diagnostic screening for rare monogenic diseases, predictive screening for common polygenic conditions, like type 1 diabetes, will be more widely implemented. The majority of the genetic background of type 1 diabetes is encoded by the HLA DQ and DR genes, selected variants of which could be used as screening markers. However, risk conferred by various HLA genotypes shows considerable ethnic variation, therefore population-specific screening markers need to be established. Aims: The aim of this study was to describe a screening strategy based on risk-defining HLA DRB1-DQA1-DQB1 markers to identify individuals at risk for type 1 diabetes in the Hungarian population. Methods: HLA genotypes of 149 consecutively diagnosed children with type 1 diabetes (age at diagnosis 0-14, mean 8.8 ± 4.2 years) and 177 randomly selected healthy schoolchildren were studied. Allele-specific polymerase chain reaction method was used for HLA typing. The diagnostic sensitivity, specificity and predictive value of diabetes associated DRB1-DQA1-DQB1 alleles were analysed in a step-wise strategy. Results: The highest diagnostic sensitivity was detected when DQB1 typing was complemented by DQA1 typing on DQB1*0201 positive samples with additional DRB1*04 subtyping in DQB1*0302 carriers. The combination of the following markers gave a relative risk of 28.9 (95{\%} confidence interval: 15.9-52.7, p = 10 -6): DQB1*0201/0302-DQA1*0301,0501-b (b ≠ DRB1* 0403), DQB1*0302/x-DRB1*0401,0402 (≠ DQB1*0201, 0301,0602,0603), DQB1*0301/0302-DRB1*0401,0404, DQB1*0304/s (s = any DQB1 alleles), DQB1*0201/y-DQA1*0501/a (y ≠ DQB1*0301,0302,0602, 0603,0604, a ≠ DQA1*0201). The diagnostic sensitivity, specificity and positive predictive values for this marker combination were 79.2{\%}, 88.7{\%}, and 1.1{\%}, respectively. Conclusions: Using HLA DRB1-DQA1-DQB1 markers predictive genetic screening for type 1 diabetes is feasible in the Hungarian population with high diagnostic sensitivity and specificity. At present, such a screening for individuals at risk for type 1 diabetes in the general population is recommended only as part of prospective studies on the natural history or prevention of disease. To increase the positive predictive value of the model, pancreas β-cell autoantibodies need to be measured and followed in the high-risk cohort.",
keywords = "Genetic screening, HLA, Prediction, Type 1 diabetes",
author = "R{\'o}bert Hermann and G. Solt{\'e}sz",
year = "2004",
month = "2",
language = "Hungarian",
volume = "145",
pages = "337--342",
journal = "Orvosi Hetilap",
issn = "0030-6002",
publisher = "Akademiai Kiado",
number = "7",

}

TY - JOUR

T1 - Az 1-es típusú diabetes és a prediktív genetikai szurés lehetoségei a magyar populációban

AU - Hermann, Róbert

AU - Soltész, G.

PY - 2004/2

Y1 - 2004/2

N2 - Introduction: In the modern genetic era the principles of genetic screening are being changed. In addition to diagnostic screening for rare monogenic diseases, predictive screening for common polygenic conditions, like type 1 diabetes, will be more widely implemented. The majority of the genetic background of type 1 diabetes is encoded by the HLA DQ and DR genes, selected variants of which could be used as screening markers. However, risk conferred by various HLA genotypes shows considerable ethnic variation, therefore population-specific screening markers need to be established. Aims: The aim of this study was to describe a screening strategy based on risk-defining HLA DRB1-DQA1-DQB1 markers to identify individuals at risk for type 1 diabetes in the Hungarian population. Methods: HLA genotypes of 149 consecutively diagnosed children with type 1 diabetes (age at diagnosis 0-14, mean 8.8 ± 4.2 years) and 177 randomly selected healthy schoolchildren were studied. Allele-specific polymerase chain reaction method was used for HLA typing. The diagnostic sensitivity, specificity and predictive value of diabetes associated DRB1-DQA1-DQB1 alleles were analysed in a step-wise strategy. Results: The highest diagnostic sensitivity was detected when DQB1 typing was complemented by DQA1 typing on DQB1*0201 positive samples with additional DRB1*04 subtyping in DQB1*0302 carriers. The combination of the following markers gave a relative risk of 28.9 (95% confidence interval: 15.9-52.7, p = 10 -6): DQB1*0201/0302-DQA1*0301,0501-b (b ≠ DRB1* 0403), DQB1*0302/x-DRB1*0401,0402 (≠ DQB1*0201, 0301,0602,0603), DQB1*0301/0302-DRB1*0401,0404, DQB1*0304/s (s = any DQB1 alleles), DQB1*0201/y-DQA1*0501/a (y ≠ DQB1*0301,0302,0602, 0603,0604, a ≠ DQA1*0201). The diagnostic sensitivity, specificity and positive predictive values for this marker combination were 79.2%, 88.7%, and 1.1%, respectively. Conclusions: Using HLA DRB1-DQA1-DQB1 markers predictive genetic screening for type 1 diabetes is feasible in the Hungarian population with high diagnostic sensitivity and specificity. At present, such a screening for individuals at risk for type 1 diabetes in the general population is recommended only as part of prospective studies on the natural history or prevention of disease. To increase the positive predictive value of the model, pancreas β-cell autoantibodies need to be measured and followed in the high-risk cohort.

AB - Introduction: In the modern genetic era the principles of genetic screening are being changed. In addition to diagnostic screening for rare monogenic diseases, predictive screening for common polygenic conditions, like type 1 diabetes, will be more widely implemented. The majority of the genetic background of type 1 diabetes is encoded by the HLA DQ and DR genes, selected variants of which could be used as screening markers. However, risk conferred by various HLA genotypes shows considerable ethnic variation, therefore population-specific screening markers need to be established. Aims: The aim of this study was to describe a screening strategy based on risk-defining HLA DRB1-DQA1-DQB1 markers to identify individuals at risk for type 1 diabetes in the Hungarian population. Methods: HLA genotypes of 149 consecutively diagnosed children with type 1 diabetes (age at diagnosis 0-14, mean 8.8 ± 4.2 years) and 177 randomly selected healthy schoolchildren were studied. Allele-specific polymerase chain reaction method was used for HLA typing. The diagnostic sensitivity, specificity and predictive value of diabetes associated DRB1-DQA1-DQB1 alleles were analysed in a step-wise strategy. Results: The highest diagnostic sensitivity was detected when DQB1 typing was complemented by DQA1 typing on DQB1*0201 positive samples with additional DRB1*04 subtyping in DQB1*0302 carriers. The combination of the following markers gave a relative risk of 28.9 (95% confidence interval: 15.9-52.7, p = 10 -6): DQB1*0201/0302-DQA1*0301,0501-b (b ≠ DRB1* 0403), DQB1*0302/x-DRB1*0401,0402 (≠ DQB1*0201, 0301,0602,0603), DQB1*0301/0302-DRB1*0401,0404, DQB1*0304/s (s = any DQB1 alleles), DQB1*0201/y-DQA1*0501/a (y ≠ DQB1*0301,0302,0602, 0603,0604, a ≠ DQA1*0201). The diagnostic sensitivity, specificity and positive predictive values for this marker combination were 79.2%, 88.7%, and 1.1%, respectively. Conclusions: Using HLA DRB1-DQA1-DQB1 markers predictive genetic screening for type 1 diabetes is feasible in the Hungarian population with high diagnostic sensitivity and specificity. At present, such a screening for individuals at risk for type 1 diabetes in the general population is recommended only as part of prospective studies on the natural history or prevention of disease. To increase the positive predictive value of the model, pancreas β-cell autoantibodies need to be measured and followed in the high-risk cohort.

KW - Genetic screening

KW - HLA

KW - Prediction

KW - Type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=2342565240&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2342565240&partnerID=8YFLogxK

M3 - Article

C2 - 15049049

AN - SCOPUS:2342565240

VL - 145

SP - 337

EP - 342

JO - Orvosi Hetilap

JF - Orvosi Hetilap

SN - 0030-6002

IS - 7

ER -