Meta-analyses Of Association Studies Between PDCD1 Gene And SLE, VDR Gene And Psoriasis

Partâ… Association between the PD1.3A/G polymorphism of the PDCD1 gene and Systemic Lupus Erythematosus:a meta-analysisBackgrounds Systemic lupus erythematosus(systemiclupuserythematosus,SLE, OMIM 152700) is a complex autoimmune disease,with contributions anticipated from genetic factors,environment,immune system disorders,sex hormones and other factors,and the genetic factors may be the root cause of the incidence of SLE. Through the use of whole-genome scan strategy,SLEB1-12 were identified as the susceptible loci.It is known that programmed cell death 1(PDCD1) gene locates in SLEB2.So far,the association of PDCD1 polymorphism(PD1.3A/G) with SLE has been widely investigated,but there are no unambiguous conclusions.Objectives To assess the combined evidence for the association between PD1.3A/G polymorphism and SLE,and to summarize the effect size of the polymorphism associated with susceptibility to SLE.Methods We surveyed studies on the PD1.3A/G polymorphism and SLE using comprehensive PubMed search up to May 2008.The retrieved literatures were screened according to the criteria and the eligible papers were entered into our study. Subsequently,the key data were extracted from each included study.Through sensitivity analysis,heterogeneity in the meta-analysis was assessed,and the source of which was also explored.A fixed-or random-effect model was choosed in the stratified meta-analysis based upon the heterogeneity analysis to calculate the combined odds ratio(OR),while publication bias was examined by funnel plot and Egger's test.We also computed the power for a given number of samples.Results A total of 20 datasets from 8 studies that met our inclusion criteria were included,15 of which were come from Europe and comprised of a total of 1 837 cases and 3 001 controls.Stratified meta-analysis demonstrated a significant association between PD1.3A and SLE among non-Spanish European descents(OR=1.290,95% CI=1.098-1.516;z=3.10,P=0.002),while a negative association was observed in Spanish population(OR=0.707,95%CI=0.537-0.930;z=2.48,P=0.013),that is, PG1.3G is the risk allele in the latter population(OR=1.414,95%CI=1.075-1.862; z=2.48,P=0.013).Both results have sufficient power to support these findings,and no publication bias presented in the studies analyzed.Conclusions This meta-analysis demonstrates a significant association between PDCD1 gene PD1.3A and SLE among non-Spanish European descents,while PD1.3G correlates with SLE susceptibility in Spanish population.PDCD1 gene may be a candidate gene of Systemic Lupus Erythematosus. Partâ…¡BsmI,TaqI,ApaI and FokI polymorphisms in the vitamin D receptor(VDR) gene and the risk of psoriasis:a meta-analysisBackgrounds 1,25-dihydroxyvitamin D₃[1,25(OH)₂D₃]and its analogs are effective for the treatment of psoriasis.Through the vitamin D receptor(VDR), 1,25(OH)₂D₃ inhibits proliferation and induces terminal differentiation of cultured human keratinocytes,and also modulate the immune system in a variety of ways.So far,most of the genetic studies that have investigated the association between psoriasis and VDR gene were performed in 4 polymorphisms:ApaI,BsmI,FokI and TaqI,but the results were much controversial or non-conclusive.Objectives To overcome the limitations of individual studies,a meta-analysis was conducted to assess the association between ApaI,BsmI,FokI and TaqI polymorphisms and psoriasis susceptibility.Methods All genetic association studies that investigated the association of the BsmI,TaqI,ApaI and FokI polymorphisms in the VDR gene with the development of psoriasis published before Oct 2008 were searched.All retrieved papers were selected according to the inclusion criteria and the eligibility ones were entered into our meta-analysis.For each included study,the informations,such as first author,year of publication,country where the trial was conducted,sample origin,numbers of cases and controls,and distributions of allele and genotype in both case and control groups, were extracted.For each of the 4 polymorphisms,we explored the significance of the associations for the allele contrast as well as the recessive and dominant models,and for each genetic contrast,in addition to the analysis among overall samples,subgroup analysis according to ethnicity was also considered for Caucasian and East Asian populations in order to estimate the possible ethnic-specific effect.The pooled odds ratio(OR) was calculated using a fixed- or a random-effects model.Heterogeneity was identified by sensitivity analysis and publication bias was examined by funnel plot and Egger's test.Results A total of 9 studies that met our inclusion criteria were included.For the ApaI polymorphism,both the allele contrast a vs.A and dominant models for allele a produced significant results in Caucasians[OR_{fixed-effect model}=1.463(1.017-2.103), OR_{fixed-effect model}=1.934(1.105-3.386),respectively],and also in overall samples [OR_{fixed-effect model}=1.400(1.088-1.800),OR_{fixed-effect model}=1.853(1.181-2.908), respectively]after removing Park et al's study which accounted for the heterogeneities.Regarding TaqI polymorphism,allele contrast t vs.T produced significant result in Caucasians[OR_{fixed-effect model}=1.344(1.033-1.749)].As for the BsmI and FokI polymorphisms,allele contrast,recessive and dominant models produced non-significant results in either Caucasians,East Asians or overall samples.Conclusions It seems from our meta-analysis that ApaI,TaqI polymorphisms, rather than BsmI,FokI polymorphisms in VDR gene,correlate with psoriasis.VDR gene might be a susceptibility gene of psoriasis.