OBJECTIVE\r\nRheumatoid arthritis (RA) is an inflammatory joint disease with features of an autoimmune disease with female predominance. Candidate genes located on the X-chromosome were selected for a family trio-based association study.\r\nMETHODS\r\nA total of 1452 individuals belonging to 3 different sample sets were genotyped for 16 single-nucleotide polymorphisms (SNP) in 7 genes. The first 2 sets consisted of 100 family trios, each of French Caucasian origin, and the third of 284 additional family trios of European Caucasian origin. Subgroups were analyzed according to sex of patient and presence of anti-cyclic citrullinated peptide (anti-CCP) autoantibodies.\r\nRESULTS\r\nFour SNP were associated with RA in the first sample set and were genotyped in the second set. In combined analysis of sets 1 and 2, evidence remained for association of 3 SNP in the genes UBA1, TIMP1, and IL9R. These were again genotyped in the third sample set. Two SNP were associated with RA in the joint analysis of all samples: rs6520278 (TIMP1) was associated with RA in general (p = 0.035) and rs3093457 (IL9R) with anti-CCP-positive RA patients (p = 0.037) and male RA patients (p = 0.010). A comparison of the results with data from whole-genome association studies further supports an association of RA with TIMPL The sex-specific association of rs3093457 (IL9R) was supported by the observation that men homozygous for rs3093457-CC are at a significantly higher risk to develop RA than women (risk ratio male/female = 2.98; p = 0.048).\r\nCONCLUSION\r\nWe provide evidence for an association of at least 2 X-chromosomal genes with RA: TIMP1 (rs6520278) and IL9R (rs3093457).
%0 Journal Article
%1 Burkhardt.2009
%A Burkhardt, Jana
%A Petit-Teixeira, Elisabeth
%A Teixeira, Vitor Hugo
%A Kirsten, Holger
%A Garnier, Sophie
%A Ruehle, Sandra
%A Oeser, Christian
%A Wolfram, Grit
%A Scholz, Markus
%A Migliorini, Paola
%A Balsa, Alejandro
%A Westhovens, Renè
%A Barrera, Pilar
%A Alves, Helena
%A Pascual-Salcedo, Dora
%A Bombardieri, Stefano
%A Dequeker, Jan
%A Radstake, Timothy R.
%A van Riel, Piet
%A van de Putte, Leo,
%A Bardin, Thomas
%A Prum, Bernard
%A Buchegger-Podbielski, Ulrike
%A Emmrich, Frank
%A Melchers, Inga
%A Cornelis, François
%A Ahnert, Peter
%D 2009
%J The Journal of rheumatology
%K Arthritis,_Rheumatoid/ethnology/genetics Case-Control_Studies Chromosomes,_Human,_X/genetics Europe European_Continental_Ancestry_Group/ethnology/genetics Female France Genetic_Predisposition_to_Disease/ethnology/genetics Genotype Homozygote Humans Male Polymorphism,_Single_Nucleotide/genetics Receptors,_Interleukin-9/genetics Tissue_Inhibitor_of_Metalloproteinase-1/genetics
%N 10
%P 2149–2157
%T Association of the X-chromosomal genes TIMP1 and IL9R with rheumatoid arthritis
%V 36
%X OBJECTIVE\r\nRheumatoid arthritis (RA) is an inflammatory joint disease with features of an autoimmune disease with female predominance. Candidate genes located on the X-chromosome were selected for a family trio-based association study.\r\nMETHODS\r\nA total of 1452 individuals belonging to 3 different sample sets were genotyped for 16 single-nucleotide polymorphisms (SNP) in 7 genes. The first 2 sets consisted of 100 family trios, each of French Caucasian origin, and the third of 284 additional family trios of European Caucasian origin. Subgroups were analyzed according to sex of patient and presence of anti-cyclic citrullinated peptide (anti-CCP) autoantibodies.\r\nRESULTS\r\nFour SNP were associated with RA in the first sample set and were genotyped in the second set. In combined analysis of sets 1 and 2, evidence remained for association of 3 SNP in the genes UBA1, TIMP1, and IL9R. These were again genotyped in the third sample set. Two SNP were associated with RA in the joint analysis of all samples: rs6520278 (TIMP1) was associated with RA in general (p = 0.035) and rs3093457 (IL9R) with anti-CCP-positive RA patients (p = 0.037) and male RA patients (p = 0.010). A comparison of the results with data from whole-genome association studies further supports an association of RA with TIMPL The sex-specific association of rs3093457 (IL9R) was supported by the observation that men homozygous for rs3093457-CC are at a significantly higher risk to develop RA than women (risk ratio male/female = 2.98; p = 0.048).\r\nCONCLUSION\r\nWe provide evidence for an association of at least 2 X-chromosomal genes with RA: TIMP1 (rs6520278) and IL9R (rs3093457).
@article{Burkhardt.2009,
abstract = {OBJECTIVE\r\nRheumatoid arthritis (RA) is an inflammatory joint disease with features of an autoimmune disease with female predominance. Candidate genes located on the X-chromosome were selected for a family trio-based association study.\r\nMETHODS\r\nA total of 1452 individuals belonging to 3 different sample sets were genotyped for 16 single-nucleotide polymorphisms (SNP) in 7 genes. The first 2 sets consisted of 100 family trios, each of French Caucasian origin, and the third of 284 additional family trios of European Caucasian origin. Subgroups were analyzed according to sex of patient and presence of anti-cyclic citrullinated peptide (anti-CCP) autoantibodies.\r\nRESULTS\r\nFour SNP were associated with RA in the first sample set and were genotyped in the second set. In combined analysis of sets 1 and 2, evidence remained for association of 3 SNP in the genes UBA1, TIMP1, and IL9R. These were again genotyped in the third sample set. Two SNP were associated with RA in the joint analysis of all samples: rs6520278 (TIMP1) was associated with RA in general (p = 0.035) and rs3093457 (IL9R) with anti-CCP-positive RA patients (p = 0.037) and male RA patients (p = 0.010). A comparison of the results with data from whole-genome association studies further supports an association of RA with TIMPL The sex-specific association of rs3093457 (IL9R) was supported by the observation that men homozygous for rs3093457-CC are at a significantly higher risk to develop RA than women (risk ratio male/female = 2.98; p = 0.048).\r\nCONCLUSION\r\nWe provide evidence for an association of at least 2 X-chromosomal genes with RA: TIMP1 (rs6520278) and IL9R (rs3093457).},
added-at = {2014-10-15T15:03:42.000+0200},
author = {Burkhardt, Jana and Petit-Teixeira, Elisabeth and Teixeira, Vitor Hugo and Kirsten, Holger and Garnier, Sophie and Ruehle, Sandra and Oeser, Christian and Wolfram, Grit and Scholz, Markus and Migliorini, Paola and Balsa, Alejandro and Westhovens, Renè and Barrera, Pilar and Alves, Helena and Pascual-Salcedo, Dora and Bombardieri, Stefano and Dequeker, Jan and Radstake, Timothy R. and {van Riel}, Piet and {van de Putte, Leo} and Bardin, Thomas and Prum, Bernard and Buchegger-Podbielski, Ulrike and Emmrich, Frank and Melchers, Inga and Cornelis, François and Ahnert, Peter},
biburl = {https://www.bibsonomy.org/bibtex/2dff40e1795202b285c78a425925d638a/drtester},
interhash = {0514356727a0caf243a9114e58cceffd},
intrahash = {dff40e1795202b285c78a425925d638a},
journal = {The Journal of rheumatology},
keywords = {Arthritis,_Rheumatoid/ethnology/genetics Case-Control_Studies Chromosomes,_Human,_X/genetics Europe European_Continental_Ancestry_Group/ethnology/genetics Female France Genetic_Predisposition_to_Disease/ethnology/genetics Genotype Homozygote Humans Male Polymorphism,_Single_Nucleotide/genetics Receptors,_Interleukin-9/genetics Tissue_Inhibitor_of_Metalloproteinase-1/genetics},
number = 10,
pages = {2149–2157},
timestamp = {2014-10-15T15:03:42.000+0200},
title = {Association of the X-chromosomal genes TIMP1 and IL9R with rheumatoid arthritis},
volume = 36,
year = 2009
}