Identification of susceptibility SNPs in IL10 and IL23R-IL12RB2 for Behcet's disease in Han Chinese

Hongsong Yu; Minming Zheng; Lijun Zhang; Hua Li; Yunyun Zhu; Ling Cheng; Lin Li; Bolin Deng; Aize Kijlstra; Peizeng Yang

doi:10.1016/j.jaci.2016.05.024

Identification of susceptibility SNPs in IL10 and IL23R-IL12RB2 for Behcet's disease in Han Chinese

Hongsong Yu, Minming Zheng, Lijun Zhang, Hua Li, Yunyun Zhu, Ling Cheng, Lin Li, Bolin Deng, Aize Kijlstra, Peizeng Yang^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Although previous genome-wide association studies in various cohorts have identified several susceptibility loci underlying Behc,et's disease (BD), this has not yet led to a breakthrough in the management of BD.

Objective: This study aimed to further investigate the association of 26 candidate single nucleotide polymorphisms with previous genome-wide association studies-identified nearly positive P values (5.0 x 10(-8) <P <1.0 x 10(-5)) in Chinese Han patients with BD.

Methods: A case-control association study was performed in 1206 patients with BD and 2475 healthy controls. Genotyping was performed using iPLEX Gold genotyping assay. Gene expression and cytokine production was quantified by real-time PCR and ELISA.

Results: The results showed that significantly higher frequencies of the IL23R-IL12RB2/rs924080 TT genotype (P = 2.03 x 10(-8); odds ratio [OR] = 1.50), IL23R-IL12RB2/rs12141431 CC genotype (P = 2.18 x 10(-8); OR = 1.53), IL10/rs1800871 TT genotype (P = 5.88 s 10(-8); OR = 1.47), and IL10/rs3024490 TT genotype (P = 2.80 x 10(-5); OR = 1.34) were found in BD. Functional experiments showed an increased IL23R expression and IL-17 production in rs12141431/CC genotype carriers compared with GG genotype carriers. A decreased IL10 expression and IL-10 production was observed in rs3024490/TT genotype carriers as compared with GG genotype carriers.

Conclusions: Our findings not only confirmed the association of IL10/rs1800871 and IL23R-IL12RB2/rs924080 with BD but also identified 2 susceptibility single nucleotide polymorphisms in IL10 and IL23R-IL12RB2 (rs3024490 and rs12141431) with BD in Han Chinese.

Original language	English
Pages (from-to)	621-627
Number of pages	7
Journal	Journal of Allergy and Clinical Immunology
Volume	139
Issue number	2
DOIs	https://doi.org/10.1016/j.jaci.2016.05.024
Publication status	Published - Feb 2017

Keywords

IL23R
IL12RB2
IL10
BD
susceptibility
GENOME-WIDE ASSOCIATION
KOYANAGI-HARADA SYNDROME
GENE POLYMORPHISMS
VKH SYNDROME
POPULATION
CELLS
PROMOTES
UVEITIS
IL-23

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10.1016/j.jaci.2016.05.024

Cite this

@article{83dbcd1a59b54942a594632318574685,

title = "Identification of susceptibility SNPs in IL10 and IL23R-IL12RB2 for Behcet's disease in Han Chinese",

abstract = "Background: Although previous genome-wide association studies in various cohorts have identified several susceptibility loci underlying Behc,et's disease (BD), this has not yet led to a breakthrough in the management of BD.Objective: This study aimed to further investigate the association of 26 candidate single nucleotide polymorphisms with previous genome-wide association studies-identified nearly positive P values (5.0 x 10(-8) <P <1.0 x 10(-5)) in Chinese Han patients with BD.Methods: A case-control association study was performed in 1206 patients with BD and 2475 healthy controls. Genotyping was performed using iPLEX Gold genotyping assay. Gene expression and cytokine production was quantified by real-time PCR and ELISA.Results: The results showed that significantly higher frequencies of the IL23R-IL12RB2/rs924080 TT genotype (P = 2.03 x 10(-8); odds ratio [OR] = 1.50), IL23R-IL12RB2/rs12141431 CC genotype (P = 2.18 x 10(-8); OR = 1.53), IL10/rs1800871 TT genotype (P = 5.88 s 10(-8); OR = 1.47), and IL10/rs3024490 TT genotype (P = 2.80 x 10(-5); OR = 1.34) were found in BD. Functional experiments showed an increased IL23R expression and IL-17 production in rs12141431/CC genotype carriers compared with GG genotype carriers. A decreased IL10 expression and IL-10 production was observed in rs3024490/TT genotype carriers as compared with GG genotype carriers.Conclusions: Our findings not only confirmed the association of IL10/rs1800871 and IL23R-IL12RB2/rs924080 with BD but also identified 2 susceptibility single nucleotide polymorphisms in IL10 and IL23R-IL12RB2 (rs3024490 and rs12141431) with BD in Han Chinese.",

keywords = "IL23R, IL12RB2, IL10, BD, susceptibility, GENOME-WIDE ASSOCIATION, KOYANAGI-HARADA SYNDROME, GENE POLYMORPHISMS, VKH SYNDROME, POPULATION, CELLS, PROMOTES, UVEITIS, IL-23",

author = "Hongsong Yu and Minming Zheng and Lijun Zhang and Hua Li and Yunyun Zhu and Ling Cheng and Lin Li and Bolin Deng and Aize Kijlstra and Peizeng Yang",

year = "2017",

month = feb,

doi = "10.1016/j.jaci.2016.05.024",

language = "English",

volume = "139",

pages = "621--627",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "MOSBY-ELSEVIER",

number = "2",

}

TY - JOUR

T1 - Identification of susceptibility SNPs in IL10 and IL23R-IL12RB2 for Behcet's disease in Han Chinese

AU - Yu, Hongsong

AU - Zheng, Minming

AU - Zhang, Lijun

AU - Li, Hua

AU - Zhu, Yunyun

AU - Cheng, Ling

AU - Li, Lin

AU - Deng, Bolin

AU - Kijlstra, Aize

AU - Yang, Peizeng

PY - 2017/2

Y1 - 2017/2

N2 - Background: Although previous genome-wide association studies in various cohorts have identified several susceptibility loci underlying Behc,et's disease (BD), this has not yet led to a breakthrough in the management of BD.Objective: This study aimed to further investigate the association of 26 candidate single nucleotide polymorphisms with previous genome-wide association studies-identified nearly positive P values (5.0 x 10(-8) <P <1.0 x 10(-5)) in Chinese Han patients with BD.Methods: A case-control association study was performed in 1206 patients with BD and 2475 healthy controls. Genotyping was performed using iPLEX Gold genotyping assay. Gene expression and cytokine production was quantified by real-time PCR and ELISA.Results: The results showed that significantly higher frequencies of the IL23R-IL12RB2/rs924080 TT genotype (P = 2.03 x 10(-8); odds ratio [OR] = 1.50), IL23R-IL12RB2/rs12141431 CC genotype (P = 2.18 x 10(-8); OR = 1.53), IL10/rs1800871 TT genotype (P = 5.88 s 10(-8); OR = 1.47), and IL10/rs3024490 TT genotype (P = 2.80 x 10(-5); OR = 1.34) were found in BD. Functional experiments showed an increased IL23R expression and IL-17 production in rs12141431/CC genotype carriers compared with GG genotype carriers. A decreased IL10 expression and IL-10 production was observed in rs3024490/TT genotype carriers as compared with GG genotype carriers.Conclusions: Our findings not only confirmed the association of IL10/rs1800871 and IL23R-IL12RB2/rs924080 with BD but also identified 2 susceptibility single nucleotide polymorphisms in IL10 and IL23R-IL12RB2 (rs3024490 and rs12141431) with BD in Han Chinese.

AB - Background: Although previous genome-wide association studies in various cohorts have identified several susceptibility loci underlying Behc,et's disease (BD), this has not yet led to a breakthrough in the management of BD.Objective: This study aimed to further investigate the association of 26 candidate single nucleotide polymorphisms with previous genome-wide association studies-identified nearly positive P values (5.0 x 10(-8) <P <1.0 x 10(-5)) in Chinese Han patients with BD.Methods: A case-control association study was performed in 1206 patients with BD and 2475 healthy controls. Genotyping was performed using iPLEX Gold genotyping assay. Gene expression and cytokine production was quantified by real-time PCR and ELISA.Results: The results showed that significantly higher frequencies of the IL23R-IL12RB2/rs924080 TT genotype (P = 2.03 x 10(-8); odds ratio [OR] = 1.50), IL23R-IL12RB2/rs12141431 CC genotype (P = 2.18 x 10(-8); OR = 1.53), IL10/rs1800871 TT genotype (P = 5.88 s 10(-8); OR = 1.47), and IL10/rs3024490 TT genotype (P = 2.80 x 10(-5); OR = 1.34) were found in BD. Functional experiments showed an increased IL23R expression and IL-17 production in rs12141431/CC genotype carriers compared with GG genotype carriers. A decreased IL10 expression and IL-10 production was observed in rs3024490/TT genotype carriers as compared with GG genotype carriers.Conclusions: Our findings not only confirmed the association of IL10/rs1800871 and IL23R-IL12RB2/rs924080 with BD but also identified 2 susceptibility single nucleotide polymorphisms in IL10 and IL23R-IL12RB2 (rs3024490 and rs12141431) with BD in Han Chinese.

KW - IL23R

KW - IL12RB2

KW - IL10

KW - BD

KW - susceptibility

KW - GENOME-WIDE ASSOCIATION

KW - KOYANAGI-HARADA SYNDROME

KW - GENE POLYMORPHISMS

KW - VKH SYNDROME

KW - POPULATION

KW - CELLS

KW - PROMOTES

KW - UVEITIS

KW - IL-23

U2 - 10.1016/j.jaci.2016.05.024

DO - 10.1016/j.jaci.2016.05.024

M3 - Article

C2 - 27464962

SN - 0091-6749

VL - 139

SP - 621

EP - 627

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 2

ER -