Objective:To study the relationship between the single nucleotide polymorphisms(SNPs)of IFNGR2genes(rs9808753,rs11910627 and rs1532) and IL-12 B gene(rs2288831)and the susceptibility to hand,foot and mouth disease(HFM...Objective:To study the relationship between the single nucleotide polymorphisms(SNPs)of IFNGR2genes(rs9808753,rs11910627 and rs1532) and IL-12 B gene(rs2288831)and the susceptibility to hand,foot and mouth disease(HFMD)caused by enterovirus 71(EV71).Methods:Blood samples were collected from 145 HFMD children infected by EV71,104 children with EV71 covert infection,and 89 normal control children,followed by DNA extraction.IFNGR2 and IL-12 Bpolymorphisms were detected by imLDRTM.Results:Compared with the control group,IFNGR2rs9808753 genotype and allele distributions of EV71-infected group and EV71 covert infection group showed significant differences(P<0.05).A allele frequency in EV71-infected patients and covert EV71-infected patients was higher than that in the control group(P <0.05).While the genotype and allele frequencies of rs2288831 in IL-12 B did not show significant difference between EV71-infected groups and healthy controls.Conclusion:These findings suggested that the single nucleotide polymorphism of IFNGR2 gene site rs9808753(A/G)was associated with the susceptibility to EV71-infection,and A allele of rs9808753 might be one potential genetic susceptibility factor of EV71-infection.While the rs2288831(C/T)polymorphism of IL-12 Bdid not correlate with the susceptibility of EV71-infection.展开更多
Adamantiades-Behcet’s disease(ABD)is a chronic inflammatory multisystem disorder.Although the precise etiology is unclear,high prevalence of human leukocyte antigen(HLA)-B51 predisposition and predominantly involved ...Adamantiades-Behcet’s disease(ABD)is a chronic inflammatory multisystem disorder.Although the precise etiology is unclear,high prevalence of human leukocyte antigen(HLA)-B51 predisposition and predominantly involved T-helper type 1 cells(Th1)-type proinflammatory cytokines and extrinsic Streptococcal infection suggest a substantial association with an immunogenetic basis and strengthens the hypothesis that IL-12,a potent inducer of Th-1 immune reaction,is a putative candidate in its pathogenesis.These clinicopathological findings led us to examine interleukin 12 p40(IL-12B)promoter polymorphism,for which the 4-base pair(bp)heterozygous insertion has been shown to affect the gene transcription and subsequent protein production.We analyzed IL-12B promoter genotypes in 194 Japanese subjects(92 with ABD and 102 normal controls)-by PCR-based restriction enzyme digestion.The frequency of the insertion heterozygosity was significantly higher in patients than in controls(49/92,53.3%vs 39/102,38.2%,respectively)-Comparing these with HLA haplotype data,this trend was more significant in HLA-B51-negative patients(29/42,69.0%vs 20/50,40.0%;P=0.005).As assessed by semiquantitative reverse transcription-PCR and ELISA,stimulation with Streptococcal antigens specifically increased expression of IL-12 p40 mRNA and protein,in conjunction with IL-12 p70 induction,in peripheral blood mononuclear cells from heterozygous patients.Our results provide evidence for anti-bacterial host response toward Th1-immunity mediated by IL-12 in patients with ABD,and the possible insight into the genetic susceptibility that is independent of HLA background.展开更多
AIM To estimate prevalence and phenotypic associations of selected inflammatory bowel disease(IBD)-associated genetic variants among Sri Lankan patients. METHODS A case study of histologically confirmed ulcerative col...AIM To estimate prevalence and phenotypic associations of selected inflammatory bowel disease(IBD)-associated genetic variants among Sri Lankan patients. METHODS A case study of histologically confirmed ulcerative colitis(UC) or Crohn's disease(CD) patients with ≥ 1 year disease duration, who were compared to unrelated, gender-matched, healthy individuals as controls, was conducted at four major centers in Sri Lanka. Phenotypic data of the cases were obtained and all participants were genotyped for 16 selected genetic variants: IL12 B :rs1045431, IL23 R :rs11805303, ARPC2 :rs12612347, IRGM :rs13361189, IL26/IL22 :rs1558744, CDH1 :rs1728785, IL10 :rs3024505, FCGR2 A :rs3737240, PTGER4 :rs4613763, IL17 REL/PIM3 :rs5771069, HNF4 a :rs6017342, STAT3 :rs744166, SMURF1 :rs7809799, LAMB1 :rs886774, HLA-DRB5, DQA1, DRB1, DRA :rs9268853, MST1, UBA7, and APEH :rs9822268. The genotypes of all variants were in Hardy-Weinberg Equilibrium(P > 10^(-3)). To account for multiple hypothesis testing, P-values < 0.003 were considered significant.RESULTS A total of 415 patients and 465 controls were recruited. Out of the single nucleotide polymorphisms(SNPs) tested, the majority were not associated with IBD in Sri Lankans. Significant positive associations were noted between rs886774(LAMB1-gene) and UC(odds ratio(OR) = 1.42, P = 0.001). UC patients with rs886774 had mild disease(OR = 1.66, P < 0.001) and remained in remission(OR = 1.48, P < 0.001). A positive association was noted between rs10045431(IL 12 B gene) and upper gastrointestinal involvement in CD(OR = 4.76, P = 0.002). CONCLUSION This confirms the heterogeneity of allelic mutations in South Asians compared to Caucasians. Most SNPs and disease associations reported here have not been described in South Asians.展开更多
基金funded by National Natural Science Foundation of China(No.81460251)Appropriate technology research and development project of Guangxi Medical and Health(No.S20141401)Chairman Foundation of Guangxi(No.201417)
文摘Objective:To study the relationship between the single nucleotide polymorphisms(SNPs)of IFNGR2genes(rs9808753,rs11910627 and rs1532) and IL-12 B gene(rs2288831)and the susceptibility to hand,foot and mouth disease(HFMD)caused by enterovirus 71(EV71).Methods:Blood samples were collected from 145 HFMD children infected by EV71,104 children with EV71 covert infection,and 89 normal control children,followed by DNA extraction.IFNGR2 and IL-12 Bpolymorphisms were detected by imLDRTM.Results:Compared with the control group,IFNGR2rs9808753 genotype and allele distributions of EV71-infected group and EV71 covert infection group showed significant differences(P<0.05).A allele frequency in EV71-infected patients and covert EV71-infected patients was higher than that in the control group(P <0.05).While the genotype and allele frequencies of rs2288831 in IL-12 B did not show significant difference between EV71-infected groups and healthy controls.Conclusion:These findings suggested that the single nucleotide polymorphism of IFNGR2 gene site rs9808753(A/G)was associated with the susceptibility to EV71-infection,and A allele of rs9808753 might be one potential genetic susceptibility factor of EV71-infection.While the rs2288831(C/T)polymorphism of IL-12 Bdid not correlate with the susceptibility of EV71-infection.
文摘Adamantiades-Behcet’s disease(ABD)is a chronic inflammatory multisystem disorder.Although the precise etiology is unclear,high prevalence of human leukocyte antigen(HLA)-B51 predisposition and predominantly involved T-helper type 1 cells(Th1)-type proinflammatory cytokines and extrinsic Streptococcal infection suggest a substantial association with an immunogenetic basis and strengthens the hypothesis that IL-12,a potent inducer of Th-1 immune reaction,is a putative candidate in its pathogenesis.These clinicopathological findings led us to examine interleukin 12 p40(IL-12B)promoter polymorphism,for which the 4-base pair(bp)heterozygous insertion has been shown to affect the gene transcription and subsequent protein production.We analyzed IL-12B promoter genotypes in 194 Japanese subjects(92 with ABD and 102 normal controls)-by PCR-based restriction enzyme digestion.The frequency of the insertion heterozygosity was significantly higher in patients than in controls(49/92,53.3%vs 39/102,38.2%,respectively)-Comparing these with HLA haplotype data,this trend was more significant in HLA-B51-negative patients(29/42,69.0%vs 20/50,40.0%;P=0.005).As assessed by semiquantitative reverse transcription-PCR and ELISA,stimulation with Streptococcal antigens specifically increased expression of IL-12 p40 mRNA and protein,in conjunction with IL-12 p70 induction,in peripheral blood mononuclear cells from heterozygous patients.Our results provide evidence for anti-bacterial host response toward Th1-immunity mediated by IL-12 in patients with ABD,and the possible insight into the genetic susceptibility that is independent of HLA background.
基金Supported by National Research Council,Sri Lanka,Grant No.NRC 13-108
文摘AIM To estimate prevalence and phenotypic associations of selected inflammatory bowel disease(IBD)-associated genetic variants among Sri Lankan patients. METHODS A case study of histologically confirmed ulcerative colitis(UC) or Crohn's disease(CD) patients with ≥ 1 year disease duration, who were compared to unrelated, gender-matched, healthy individuals as controls, was conducted at four major centers in Sri Lanka. Phenotypic data of the cases were obtained and all participants were genotyped for 16 selected genetic variants: IL12 B :rs1045431, IL23 R :rs11805303, ARPC2 :rs12612347, IRGM :rs13361189, IL26/IL22 :rs1558744, CDH1 :rs1728785, IL10 :rs3024505, FCGR2 A :rs3737240, PTGER4 :rs4613763, IL17 REL/PIM3 :rs5771069, HNF4 a :rs6017342, STAT3 :rs744166, SMURF1 :rs7809799, LAMB1 :rs886774, HLA-DRB5, DQA1, DRB1, DRA :rs9268853, MST1, UBA7, and APEH :rs9822268. The genotypes of all variants were in Hardy-Weinberg Equilibrium(P > 10^(-3)). To account for multiple hypothesis testing, P-values < 0.003 were considered significant.RESULTS A total of 415 patients and 465 controls were recruited. Out of the single nucleotide polymorphisms(SNPs) tested, the majority were not associated with IBD in Sri Lankans. Significant positive associations were noted between rs886774(LAMB1-gene) and UC(odds ratio(OR) = 1.42, P = 0.001). UC patients with rs886774 had mild disease(OR = 1.66, P < 0.001) and remained in remission(OR = 1.48, P < 0.001). A positive association was noted between rs10045431(IL 12 B gene) and upper gastrointestinal involvement in CD(OR = 4.76, P = 0.002). CONCLUSION This confirms the heterogeneity of allelic mutations in South Asians compared to Caucasians. Most SNPs and disease associations reported here have not been described in South Asians.
