diabetic nephropathy ( dn ) is a major cause of end - stage renal disease ( esrd ) and high mortality in diabetic patients .
for example , high blood pressure , high glomerular filtration rate , glycemic control , and race were reported to be associated with dn development .
genetic susceptibility may also be an important determinant of the incidence and severity of dn .
interleukin-10 ( il-10 ) is an immunoregulatory cytokine produced by th2 cells , regulatory t cells , and monocytes / macrophages .
il-10 is an anti - inflammatory cytokine that can inhibit the synthesis of cytokines such as il-6 , il-1 , il-1 , and tnf- in activated macrophage and ifn by t cells .
myliwska et al . found elevated concentration of circulating il-10 in diabetes mellitus ( dm ) patients with dn , compared to dm patients without dn .
wong et al . suggested that plasma concentrations of il-10 exhibited significant positive correlation with urine albumin / creatinine ratio in dn patients . in addition , changes in il-10 levels correlated with the extent of renal damage in dn .
taken together , these reports indicate that il-10 might contribute to the pathogenesis of dn . several previous studies have studied the association between il10 - 1082a / g polymorphism and dn risk [ 713 ] . however , the results were inconclusive and contradictory .
for example , babel et al . suggested that il10 - 1082a / g polymorphism may increase susceptibility to dn .
. concluded that the il-10 ( 1082g / a ) gene polymorphism was not associated with the development of dn in turkish patients with type 2 diabetes .
therefore , we performed a meta - analysis to investigate the association between il10 - 1082a / g polymorphism and dn risk .
all relevant studies were searched by using the pubmed and embase ( the last retrieval date was oct 10 , 2014 using the search terms :  diabetic nephropathy  and  interleukin-10  or  il10  ) .
all searched studies were retrieved and only published studies with full - text articles were included . when there were multiple publications with duplicate samples , only the newest study was used in this research .
our study was approved by the ethics committee of the first affiliated hospital of henan university of science and technology .
the inclusion criteria were : ( 1 ) the research was a case - control study or a cohort study ; ( 2 ) the study investigated the association between il10 - 1082a / g polymorphism and dn risk ; ( 3 ) the il10 - 1082a / g genotypes of individual groups were provided .
the exclusion criteria were : ( 1 ) no usable data reported ; ( 2 ) animal studies ; ( 3 ) reviews or abstracts ; ( 4 ) duplicates .
two authors extracted the data independently , including first author , year , ethnicity , age , sex , diabetes type , and sample size .
statistical analysis was conducted using stata software 11.0 ( statacorp , college station , tx , usa ) .
hardy - weinberg equilibrium ( hwe ) test in healthy control group was conducted using the  test .
odds ratio ( or ) with a 95% confidence interval ( ci ) are presented for dichotomous data , and the significance level was 0.05 .
q - statistic and i - statistic were used to measure statistical heterogeneity and the significance level was 0.10 .
a fixed - effects model was selected when there was no significant heterogeneity ; otherwise , a random - effects model was used .
publication bias was tested using begg s test and funnel plot ( significant level was 0.05 ) .
all relevant studies were searched by using the pubmed and embase ( the last retrieval date was oct 10 , 2014 using the search terms :  diabetic nephropathy  and  interleukin-10  or  il10  ) .
all searched studies were retrieved and only published studies with full - text articles were included . when there were multiple publications with duplicate samples , only the newest study was used in this research .
our study was approved by the ethics committee of the first affiliated hospital of henan university of science and technology .
the inclusion criteria were : ( 1 ) the research was a case - control study or a cohort study ; ( 2 ) the study investigated the association between il10 - 1082a / g polymorphism and dn risk ; ( 3 ) the il10 - 1082a / g genotypes of individual groups were provided .
the exclusion criteria were : ( 1 ) no usable data reported ; ( 2 ) animal studies ; ( 3 ) reviews or abstracts ; ( 4 ) duplicates .
two authors extracted the data independently , including first author , year , ethnicity , age , sex , diabetes type , and sample size .
statistical analysis was conducted using stata software 11.0 ( statacorp , college station , tx , usa ) .
hardy - weinberg equilibrium ( hwe ) test in healthy control group was conducted using the  test .
odds ratio ( or ) with a 95% confidence interval ( ci ) are presented for dichotomous data , and the significance level was 0.05 .
q - statistic and i - statistic were used to measure statistical heterogeneity and the significance level was 0.10 .
a fixed - effects model was selected when there was no significant heterogeneity ; otherwise , a random - effects model was used .
publication bias was tested using begg s test and funnel plot ( significant level was 0.05 ) .
two studies were conducted in asian populations and the rest of the studies were performed in caucasian populations .
thus , a total of 9 case - control studies with 4165 subjects were included in this meta - analysis [ 713 ] .
previous studies showed that the il10 - 1082aa genotype was associated with increased il-10 production .
therefore , we investigated the association between il10 - 1082a / g polymorphism and dn risk in the recessive models ( aa vs. ga+gg ) .
we found that il10 - 1082a / g polymorphism significantly associated with an increased dn risk ( or=1.21 ; 95% ci 1.071.37 ; p=0.002 ; figure 1 ) . in the subgroup analysis by race
, both caucasians and asians with il10 - 1082a / g polymorphism showed increased dn risk ( or=1.25 ; 95% ci 1.031.52 ; p=0.03 and or=1.25 ; 95% ci 1.041.49 ; p=0.02 ) , respectively .
when we deleted the study without dm type , the result was not altered ( or=1.21 ; 95% ci 1.021.44 ; p=0.03 ) . in the subgroup analysis by sample size , studies with large sample size and studies with small sample size both showed increased dn risk ( or=1.16 ; 95% ci 1.021.31 ; p=0.02 and or=1.50 ; 95% ci 1.141.98 ; p=0.004 ) , respectively .
cumulative meta - analysis was conducted by sorting the studies by publication time ( figure 2 ) . to determine the stability of the result
we found that no single study impacted the pooled or , indicating that the results of our research are statistically robust ( figure 3 ) .
egger s test and begg s funnel plot were conducted to assess the publication bias .
two studies were conducted in asian populations and the rest of the studies were performed in caucasian populations .
thus , a total of 9 case - control studies with 4165 subjects were included in this meta - analysis [ 713 ] .
previous studies showed that the il10 - 1082aa genotype was associated with increased il-10 production .
therefore , we investigated the association between il10 - 1082a / g polymorphism and dn risk in the recessive models ( aa vs. ga+gg ) .
we found that il10 - 1082a / g polymorphism significantly associated with an increased dn risk ( or=1.21 ; 95% ci 1.071.37 ; p=0.002 ; figure 1 ) . in the subgroup analysis by race
, both caucasians and asians with il10 - 1082a / g polymorphism showed increased dn risk ( or=1.25 ; 95% ci 1.031.52 ; p=0.03 and or=1.25 ; 95% ci 1.041.49 ; p=0.02 ) , respectively .
when we deleted the study without dm type , the result was not altered ( or=1.21 ; 95% ci 1.021.44 ; p=0.03 ) . in the subgroup analysis by sample size ,
studies with large sample size and studies with small sample size both showed increased dn risk ( or=1.16 ; 95% ci 1.021.31 ; p=0.02 and or=1.50 ; 95% ci 1.141.98 ; p=0.004 ) , respectively .
cumulative meta - analysis was conducted by sorting the studies by publication time ( figure 2 ) . to determine the stability of the result
we found that no single study impacted the pooled or , indicating that the results of our research are statistically robust ( figure 3 ) .
egger s test and begg s funnel plot were conducted to assess the publication bias .
several meta - analyses have been performed to assess the association between il10 - 1082a / g polymorphism and dm risk [ 1517 ] . however , no meta - analysis study evaluated the association between il10 - 1082a / g polymorphism and dn risk .
thus , this is the first meta - analysis of the association between il10 - 1082a / g polymorphism and dn risk .
the present meta - analysis of 9 case - control studies evaluated the association between il10 - 1082a / g polymorphism and dn risk .
we found that il10 - 1082a / g polymorphism was a risk factor for dn .
this result indicates that il10 - 1082aa genotype might increase dn risk more than the ag or gg genotypes . in the race subgroup analysis , both caucasians and asians with il10 - 1082a / g polymorphism showed increased dn risk .
this result suggests that il10 - 1082a / g polymorphism played the same role in the pathological mechanism of dn in different races , but there were only 2 studies in asian populations .
we also found that il10 - 1082a / g polymorphism could increase dn in the t2 dm patients .
since no study with t1 dm was included , more studies with these populations are needed .
studies with large sample size and studies with small sample size showed increased dn risk .
this result suggests that sample size did not change the result of this meta - analysis .
considering all of these results , we confirmed that il10 - 1082a / g polymorphism might contribute to the development of dn .
a large body of evidence suggests that the pathogenesis of dm is related to the presence of a chronic low - grade inflammatory state and the activation of the innate immune system .
additionally , inflammatory cytokines were reported to be involved in the development of microvascular diabetic complications , including dn .
il-10 was a candidate gene in the pathophysiologic mechanism of auto - immune / inflammatory disease , because it could regulate both cellular and humoral immunity .
a previous study suggested that il-10 was elevated in the sera of t2 dm patients with dn .
first , the studies included in our meta - analysis were small ; therefore , our meta - analysis had low statistical power to assess the association of the il10 - 1082a / g polymorphism with the risk of dn .
second , the number of the included studies was moderate ; therefore , the results of this meta - analysis might be influenced by factors such as publication bias , but no evidence of publication bias was found in our study .
third , our study did not address gene - gene and gene - environment interactions .
last but not least , this meta - analysis lacked sufficient reliability to confirm or refute the results of subgroup analysis in a definitive manner .
our meta - analysis study confirmed that il10 - 1082a / g polymorphism might contribute to the susceptibility for dn .
 backgroundstudies have assessed the association between interleukin-10 ( il-10 ) -1082a / g polymorphism and diabetic nephropathy ( dn ) risk , but the results were inconclusive and contradictory . 
 therefore , we performed a meta - analysis to investigate the association between il10 - 1082a / g polymorphism and dn risk.material/methodsall relevant studies were searched by using pubmed and embase . 
 data were extracted by 2 authors independently . 
 odds ratios ( ors ) and corresponding 95% confidence intervals ( cis ) were calculated.resultsnine case - control studies with 4165 subjects were included in this meta - analysis . 
 we found that il10 - 1082a / g polymorphism was significantly associated with an increased dn risk ( or=1.21 ; 95% ci 1.071.37 ; p=0.002 ) . in the subgroup analysis by race 
 , both caucasians and asians with il10 - 1082a / g polymorphism showed increased dn risk ( or=1.25 ; 95% ci 1.031.52 ; p=0.03 and or=1.25 ; 95% ci 1.041.49 ; p=0.02 ) , respectively . when we deleted the study without diabetes type , the result was not altered ( or=1.21 ; 95% ci 1.021.44 ; p=0.03 ) . in the subgroup analysis by sample size , 
 both studies with large sample size and studies with small sample size showed increased dn risk ( or=1.16 ; 95% ci 1.021.31 ; p=0.02 and or=1.50 ; 95% ci 1.141.98 ; p=0.004 ) , respectively.conclusionsthis meta - analysis confirmed that il10 - 1082a / g polymorphism might contribute to the susceptibility for dn . 
Background
Material and Methods
Publication search
Inclusion and exclusion criteria
Data extraction
Statistical analysis
Results
Study characteristics
Quantitative data synthesis
Discussion
Conclusions