Association of IL23R, TNFRSF1A, and HLA-DRB1*0103 allele variants with inflammatory bowel disease phenotypes in the Finnish population

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC), 2 major forms of inflammatory bowel disease (IBD), are complex disorders with significant genetic predisposition. The first CD-associated gene, CARD15/NOD2, was recently identified and since then several reports on novel IBD candidate genes have emerged. We investigated disease phenotype association to genetic variations in IL23R, ATG16L1, DLG5, ABCB1/MDR1, TLR4, TNFRSF1A, chromosome 5 risk haplotype including SLC22A4 and SLC22A5, and HLA-DRB1*0103 allele among Finnish IBD patients.
METHODS: A total of 699 IBD patients were genotyped for disease-associated variants by polymerase chain reaction (PCR) and restriction enzyme digestion or Sequenom iPLEX method.
RESULTS: Five markers spanning the IL23R gene were associated with CD. The SNP (single nucleotide polymorphism) rs2201841 gave the strongest association (P = 0.002). The rare HLA-DRB1*0103 allele was found to associate with UC (P = 0.008), and the TNFRSF1A A36G variant was associated with familial UC (P = 0.007). Upon phenotypic analysis we detected association between familial UC and rare TNFRSF1A alleles 36G and IVS6+10G (P = 0.001 and P = 0.042, respectively). In addition, IL23R markers were associated with stricturing CD (P = 0.010-0.017), and ileocolonic CD was more prevalent in the carriers of the same 2 TNFRSF1A variants (P = 0.021 and P = 0.028, respectively). Less significant genotype-phenotype associations were observed for the TLR4 and HLA variants.
CONCLUSIONS: We were able to replicate the association of the IL23R variants with CD as well as HLA-DRB1*0103 with UC; confirmation of TNFRSF1A association with UC needs additional studies. Our findings also suggest that polymorphisms at IL23R and TNFRSF1A, and possibly HLA and TLR4, loci may account for phenotypic variation in IBD.
Alkuperäiskielienglanti
LehtiInflammatory Bowel Diseases
Vuosikerta14
Numero8
Sivut1118-1124
Sivumäärä7
ISSN1078-0998
DOI - pysyväislinkit
TilaJulkaistu - 2008
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

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@article{caf5e0f97083476da9e5146d1ad9e8e7,
title = "Association of IL23R, TNFRSF1A, and HLA-DRB1*0103 allele variants with inflammatory bowel disease phenotypes in the Finnish population",
abstract = "BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC), 2 major forms of inflammatory bowel disease (IBD), are complex disorders with significant genetic predisposition. The first CD-associated gene, CARD15/NOD2, was recently identified and since then several reports on novel IBD candidate genes have emerged. We investigated disease phenotype association to genetic variations in IL23R, ATG16L1, DLG5, ABCB1/MDR1, TLR4, TNFRSF1A, chromosome 5 risk haplotype including SLC22A4 and SLC22A5, and HLA-DRB1*0103 allele among Finnish IBD patients.METHODS: A total of 699 IBD patients were genotyped for disease-associated variants by polymerase chain reaction (PCR) and restriction enzyme digestion or Sequenom iPLEX method.RESULTS: Five markers spanning the IL23R gene were associated with CD. The SNP (single nucleotide polymorphism) rs2201841 gave the strongest association (P = 0.002). The rare HLA-DRB1*0103 allele was found to associate with UC (P = 0.008), and the TNFRSF1A A36G variant was associated with familial UC (P = 0.007). Upon phenotypic analysis we detected association between familial UC and rare TNFRSF1A alleles 36G and IVS6+10G (P = 0.001 and P = 0.042, respectively). In addition, IL23R markers were associated with stricturing CD (P = 0.010-0.017), and ileocolonic CD was more prevalent in the carriers of the same 2 TNFRSF1A variants (P = 0.021 and P = 0.028, respectively). Less significant genotype-phenotype associations were observed for the TLR4 and HLA variants.CONCLUSIONS: We were able to replicate the association of the IL23R variants with CD as well as HLA-DRB1*0103 with UC; confirmation of TNFRSF1A association with UC needs additional studies. Our findings also suggest that polymorphisms at IL23R and TNFRSF1A, and possibly HLA and TLR4, loci may account for phenotypic variation in IBD.",
keywords = "Finnish, inflammatory bowel disease, HLA-DRB1*0103, IL23R, TNFRSF1A, GENOME-WIDE ASSOCIATION, PEDIATRIC CROHNS-DISEASE, TOLL-LIKE RECEPTOR-4, CATION TRANSPORTER GENES, ULCERATIVE-COLITIS, SUSCEPTIBILITY LOCI, IBD5 LOCUS, HLA-DR, DETERMINES SUSCEPTIBILITY, FUNCTIONAL VARIANTS",
author = "Maarit Lappalainen and Leena Halme and Ulla Turunen and P{\"a}ivi Saavalainen and Elisabet Einarsdottir and Martti F{\"a}rkkil{\"a} and Kimmo Kontula and Paulina Paavola-Sakki",
year = "2008",
doi = "10.1002/ibd.20431",
language = "English",
volume = "14",
pages = "1118--1124",
journal = "Inflammatory Bowel Diseases",
issn = "1078-0998",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - Association of IL23R, TNFRSF1A, and HLA-DRB1*0103 allele variants with inflammatory bowel disease phenotypes in the Finnish population

AU - Lappalainen, Maarit

AU - Halme, Leena

AU - Turunen, Ulla

AU - Saavalainen, Päivi

AU - Einarsdottir, Elisabet

AU - Färkkilä, Martti

AU - Kontula, Kimmo

AU - Paavola-Sakki, Paulina

PY - 2008

Y1 - 2008

N2 - BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC), 2 major forms of inflammatory bowel disease (IBD), are complex disorders with significant genetic predisposition. The first CD-associated gene, CARD15/NOD2, was recently identified and since then several reports on novel IBD candidate genes have emerged. We investigated disease phenotype association to genetic variations in IL23R, ATG16L1, DLG5, ABCB1/MDR1, TLR4, TNFRSF1A, chromosome 5 risk haplotype including SLC22A4 and SLC22A5, and HLA-DRB1*0103 allele among Finnish IBD patients.METHODS: A total of 699 IBD patients were genotyped for disease-associated variants by polymerase chain reaction (PCR) and restriction enzyme digestion or Sequenom iPLEX method.RESULTS: Five markers spanning the IL23R gene were associated with CD. The SNP (single nucleotide polymorphism) rs2201841 gave the strongest association (P = 0.002). The rare HLA-DRB1*0103 allele was found to associate with UC (P = 0.008), and the TNFRSF1A A36G variant was associated with familial UC (P = 0.007). Upon phenotypic analysis we detected association between familial UC and rare TNFRSF1A alleles 36G and IVS6+10G (P = 0.001 and P = 0.042, respectively). In addition, IL23R markers were associated with stricturing CD (P = 0.010-0.017), and ileocolonic CD was more prevalent in the carriers of the same 2 TNFRSF1A variants (P = 0.021 and P = 0.028, respectively). Less significant genotype-phenotype associations were observed for the TLR4 and HLA variants.CONCLUSIONS: We were able to replicate the association of the IL23R variants with CD as well as HLA-DRB1*0103 with UC; confirmation of TNFRSF1A association with UC needs additional studies. Our findings also suggest that polymorphisms at IL23R and TNFRSF1A, and possibly HLA and TLR4, loci may account for phenotypic variation in IBD.

AB - BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC), 2 major forms of inflammatory bowel disease (IBD), are complex disorders with significant genetic predisposition. The first CD-associated gene, CARD15/NOD2, was recently identified and since then several reports on novel IBD candidate genes have emerged. We investigated disease phenotype association to genetic variations in IL23R, ATG16L1, DLG5, ABCB1/MDR1, TLR4, TNFRSF1A, chromosome 5 risk haplotype including SLC22A4 and SLC22A5, and HLA-DRB1*0103 allele among Finnish IBD patients.METHODS: A total of 699 IBD patients were genotyped for disease-associated variants by polymerase chain reaction (PCR) and restriction enzyme digestion or Sequenom iPLEX method.RESULTS: Five markers spanning the IL23R gene were associated with CD. The SNP (single nucleotide polymorphism) rs2201841 gave the strongest association (P = 0.002). The rare HLA-DRB1*0103 allele was found to associate with UC (P = 0.008), and the TNFRSF1A A36G variant was associated with familial UC (P = 0.007). Upon phenotypic analysis we detected association between familial UC and rare TNFRSF1A alleles 36G and IVS6+10G (P = 0.001 and P = 0.042, respectively). In addition, IL23R markers were associated with stricturing CD (P = 0.010-0.017), and ileocolonic CD was more prevalent in the carriers of the same 2 TNFRSF1A variants (P = 0.021 and P = 0.028, respectively). Less significant genotype-phenotype associations were observed for the TLR4 and HLA variants.CONCLUSIONS: We were able to replicate the association of the IL23R variants with CD as well as HLA-DRB1*0103 with UC; confirmation of TNFRSF1A association with UC needs additional studies. Our findings also suggest that polymorphisms at IL23R and TNFRSF1A, and possibly HLA and TLR4, loci may account for phenotypic variation in IBD.

KW - Finnish

KW - inflammatory bowel disease

KW - HLA-DRB10103

KW - IL23R

KW - TNFRSF1A

KW - GENOME-WIDE ASSOCIATION

KW - PEDIATRIC CROHNS-DISEASE

KW - TOLL-LIKE RECEPTOR-4

KW - CATION TRANSPORTER GENES

KW - ULCERATIVE-COLITIS

KW - SUSCEPTIBILITY LOCI

KW - IBD5 LOCUS

KW - HLA-DR

KW - DETERMINES SUSCEPTIBILITY

KW - FUNCTIONAL VARIANTS

U2 - 10.1002/ibd.20431

DO - 10.1002/ibd.20431

M3 - Article

VL - 14

SP - 1118

EP - 1124

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

IS - 8

ER -