crohn 's disease ( cd ) is a form of inflammatory bowel disease ( ibd ) that primarily affects the caucasian population [ 1 , 2 ] .
therefore , identification of gene risk factors of cd is beneficial for the clinical treatment of patients .
interleukin 23 ( il-23 ) plays an important role in the inflammatory response against infection as a regulator of immune cells .
il-23r which interacts with il-23 is a protein consisting of an il-121 and an il-23r chain .
recently , the mechanisms of il-23r variants have been investigated in different autoimmune diseases [ 69 ] .
studies also have shown that rs7517847 , the single nucleotide polymorphisms ( snps ) of the il23r gene , are associated with cd occurring rate [ 10 , 11 ] .
however , the association between il-23r polymorphisms and cd susceptibility are inconclusive and controversial due to small sample size in each of the published studies . to better understand the association of il-23r polymorphisms and cd susceptibility in caucasians
, we conducted a meta - analysis of all eligible studies and hope to yield more accurate and robust estimates .
available studies for il-23r polymorphism and cd were collected by different combinations of various key words : interleukin-23 receptor , il-23r ; polymorphism , variant , or mutation ; crohn 's disease , cd .
languages restriction was not imposed in this research and only published studies with full text were included in this meta - analysis . in the meta - analysis ,
the following inclusive selection criteria were set : ( a ) study design evaluating the association between il-23r polymorphism and cd risk ; ( b ) case control design ; ( c ) caucasians design .
the following exclusive selection criteria were set : ( a ) no control cases ; ( b ) duplication of the previous publication ; ( c ) no available genotype frequency ; for studies with overlapped or repeated data ( d ) no caucasians .
eligible studies were extracted by 2 reviewers ( li zhang and yunjie lu ) independently according to the predesigned data collection form .
the following information was extracted : first author 's name , publication year , country , ethnicity , immune suppressive protocol , number of cases and controls , and genotype distribution in both groups .
disagreement was resolved by discussion with a third reviewer ( guozhong yao ) . for each trial ,
odds ratio ( or ) with the 95% confidence interval ( 95% ci ) of the survival rate was derived and calculated . increased or decreased risk of cd
the pooled ors were estimated for allelic model ( t allele versus g allele ) , homozygote comparison ( tt versus gg ) and heterozygote comparison ( tg versus gg ) , dominant models ( tt / tg versus gg ) , and recessive model ( tt versus tg+gg ) .
z test was performed to assess the significance of the pooled or . between - study
the random effects model was conducted if the q test exhibited a p < 0.05 or the i test showed > 50% .
the begg 's funnel plot and egger 's linear regression test were conducted , and p < 0.05 was considered significant . a fixed - effect model ( based on mantel - haenszel method )
was utilized to pool the data from different studies if the between - study heterogeneity was absent , or a random - effect model ( based on dersimonian and laird method ) was applied .
the statistical analysis was performed by stata 10.0 ( stata corp lp , college station , tx , usa ) .
a total of 133 studies were identified by our first research ; a number of 41 were preliminarily yielded out after excluding inappropriate studies and screening abstract - screening , full - text assessment . in these 41 studies ,
30 were excluded , 11 articles containing rs7517847 in caucasians were recruited for detailed analysis ( table 1 ) , and these data built table 1 [ 1323 ] .
thus , a total of 3279 cd cases and 4136 healthy controls were included in our meta - analysis .
all of them were caucasian and the diagnosis of cd was based on clinical manifestations and laboratory examinations and further biopsy .
after pooling all the eligible studies in table 2 , we found that the risk of cd was significantly associated with rs7517847 in dominant models ( tt / tg versus gg : or = 1.652 , 95% ci 1.277 , 2.137 ) , allelic model ( t allele versus g allele : or = 1.327 , 95% ci 1.198 , 1.469 ) , homozygote comparison ( tt versus gg : or = 1.890 , 95% ci 1.465 , 2.437 , figure 2 ) , heterozygote comparison ( tg versus gg : or = 1.509 , 95% ci 1.161 , 1.960 ) , and recessive model ( tt versus tg / gg : or = 1.409 , 95% ci 1.279 , 1.552 ) .
these data demonstrate that rs7517847 increases the risk of cd among caucasians with hospital - based studies .
begg 's funnel plot and egger 's test were both performed to assess the publication bias of this meta - analysis .
the shape of the funnel plots for homozygote comparison models seemed symmetrical ( figure 3 ) .
then , the egger 's test was used to provide statistical evidence of funnel plot symmetry .
cd is associated with jak2 signaling pathway which is activated by il-23 and il-23r receptor .
previous studies suggested that the interruption of il-23r snps might lead to the dysregulation of intestinal inflammation .
il-23r gene variants also play an essential role in the development of many autoimmune diseases such as ankylosing spondylitis ( as ) , inflammatory bowel disease ( ibd ) , and systemic lupus erythematosus ( sle ) [ 7 , 26 , 27 ] .
therefore , researchers are focusing on observing the relationship between il-23r gene polymorphisms and the risk of cd .
however , the results are conflicting and controversial due to the different races and insufficient sample size . after pooling data for 11 studies in this meta - analysis ,
our results firstly demonstrate that t allele of rs7517847 was highly susceptible to cd in caucasians .
one previous study showed that rs7517847 is a protective factor in rheumatoid arthritis ( ra ) in european population .
interestingly , ra is a systemic autoinflammatory disease which is associated with ptpn22/c1858 t , while the organ - specific autoimmune disease cd is not [ 28 , 29 ] .
thus , the mechanism of this genetic variant may not play a common role in different autoimmune diseases .
secondly , publication bias might occur even if there is no significance in statistical test due to extracting published studies . ultimately , owing to methodological limitations , this meta - analysis is retrospective .
two independent authors performed the process of study selection and data extraction and a third author resolved the discrepancy to minimize the bias . in conclusion
, our meta - analysis suggests that il-23r rs7517847 confers susceptibility to cd in the caucasians .
 the association between interleukin-23r gene polymorphism and crohn 's disease ( cd ) in caucasians is still controversial . 
 thus , a meta - analysis was performed to evaluate the correlation between this gene variant and cd risk . 
 we retrieved the available data from embase and pubmed until may 1 , 2014 , and evaluated the effect of rs7517847 in caucasians . 
 the significant associations were confirmed between rs7517847 and cd risk in dominant models ( tt / tg versus gg : or = 1.652 , 95% ci 1.277 , 2.137 ) , allelic model ( t allele versus g allele : or = 1.327 , 95% ci 1.198 , 1.469 ) , homozygote comparison ( tt versus gg : or = 1.890 , 95% ci 1.465 , 2.437 ) , heterozygote comparison ( tg versus gg : or = 1.509 , 95% ci 1.161 , 1.960 ) , and recessive model ( tt versus tg / gg : or = 1.409 , 95% ci 1.279 , 1.552 ) . in conclusion , this meta - analysis demonstrates that rs7517847 is associated with the risk of cd in caucasians . 
 these findings show that il-23r genes confer susceptibility to cd in the caucasians . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussion