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Tagging single nucleotide polymorphisms in the IRF1 and IRF8 genes and tuberculosis susceptibility.

Ding S, Jiang T, He J, Qin B, Lin S, Li L - PLoS ONE (2012)

Bottom Line: In the IRF8 gene, interestingly, we found that three tagSNPs (rs925994 and rs11117415 located in the intron region; rs10514611 located in the 3'UTR) were associated with risk of tuberculosis after Bonferroni correction.Per allele OR was 1.75 (95% CI 1.35 ~ 2.27, P = 0.002), 4.75 (95% CI 2.16 ~ 10.43, P = 0.002) and 3.39 (95% CI 1.60 ~ 7.20, P = 0.015) respectively.Luciferase reporter gene assay showed that the construct that contained the non-risk allele C of rs10514611 showed significantly higher luciferase activity than did the risk T allele (P<0.01), which implied rs10514611 was a potential functional SNP site.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, China.

ABSTRACT
Genes encoding IRF1 and IRF8 protein have been proposed as candidate tuberculosis susceptibility genes. In order to elucidate whether the IRF1 and IRF8 variants were associated with tuberculosis susceptibility, we conducted a case-control study consisting of 495 controls and 452 ethnically matched cases with tuberculosis in a Chinese population. Seven haplotype tagging single-nucleotide polymorphisms (tagSNPs) (rs2057656; rs2706381; rs2070724; rs2070721; rs2549008; rs2549007; rs2706386) from HapMap database were analyzed, which provided an almost complete coverage of the genetic variations in the IRF1 gene. Fifteen tagSNPs (rs12924316; rs182511; rs305080; rs2292980; rs925994; rs424971; rs16939967; rs11117415; rs4843860; rs9926411; rs8064189; rs12929551; rs10514611; rs1044873; rs6638) were observed in the IRF8 gene. All these tagSNPs were genotyped by SNPstream genotyping and SNaPshot typing. None of the seven tagSNPs was individually associated with tuberculosis in the IRF1 gene. In the IRF8 gene, interestingly, we found that three tagSNPs (rs925994 and rs11117415 located in the intron region; rs10514611 located in the 3'UTR) were associated with risk of tuberculosis after Bonferroni correction. Per allele OR was 1.75 (95% CI 1.35 ~ 2.27, P = 0.002), 4.75 (95% CI 2.16 ~ 10.43, P = 0.002) and 3.39 (95% CI 1.60 ~ 7.20, P = 0.015) respectively. Luciferase reporter gene assay showed that the construct that contained the non-risk allele C of rs10514611 showed significantly higher luciferase activity than did the risk T allele (P<0.01), which implied rs10514611 was a potential functional SNP site. Our results indicated that the IRF8 gene might participate in genetic susceptibility to tuberculosis in a Chinese population.

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Related in: MedlinePlus

Linkage disequilibrium statistic (r2) for the IRF8 gene.(Genomic organization of the IRF8 gene, including the position of individual non-coding (open boxes) and coding (closed boxes) exons; the darker shading indicates stronger LD between SNPs).
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pone-0042104-g002: Linkage disequilibrium statistic (r2) for the IRF8 gene.(Genomic organization of the IRF8 gene, including the position of individual non-coding (open boxes) and coding (closed boxes) exons; the darker shading indicates stronger LD between SNPs).

Mentions: Table 4 showed the primary information for the fifteen tagSNPs in the IRF8 gene. The genotype distributions of the fifteen studied tagSNPs were in Hardy-Weinberg equilibrium (all P>0.05) among the subjects except for rs424971 (P<0.01). The linkage disequilibrium between tagSNP pairs was shown in Figure 2. According to r2 value, the fourteen tagSNPs could be represented for the whole gene.


Tagging single nucleotide polymorphisms in the IRF1 and IRF8 genes and tuberculosis susceptibility.

Ding S, Jiang T, He J, Qin B, Lin S, Li L - PLoS ONE (2012)

Linkage disequilibrium statistic (r2) for the IRF8 gene.(Genomic organization of the IRF8 gene, including the position of individual non-coding (open boxes) and coding (closed boxes) exons; the darker shading indicates stronger LD between SNPs).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3412841&req=5

pone-0042104-g002: Linkage disequilibrium statistic (r2) for the IRF8 gene.(Genomic organization of the IRF8 gene, including the position of individual non-coding (open boxes) and coding (closed boxes) exons; the darker shading indicates stronger LD between SNPs).
Mentions: Table 4 showed the primary information for the fifteen tagSNPs in the IRF8 gene. The genotype distributions of the fifteen studied tagSNPs were in Hardy-Weinberg equilibrium (all P>0.05) among the subjects except for rs424971 (P<0.01). The linkage disequilibrium between tagSNP pairs was shown in Figure 2. According to r2 value, the fourteen tagSNPs could be represented for the whole gene.

Bottom Line: In the IRF8 gene, interestingly, we found that three tagSNPs (rs925994 and rs11117415 located in the intron region; rs10514611 located in the 3'UTR) were associated with risk of tuberculosis after Bonferroni correction.Per allele OR was 1.75 (95% CI 1.35 ~ 2.27, P = 0.002), 4.75 (95% CI 2.16 ~ 10.43, P = 0.002) and 3.39 (95% CI 1.60 ~ 7.20, P = 0.015) respectively.Luciferase reporter gene assay showed that the construct that contained the non-risk allele C of rs10514611 showed significantly higher luciferase activity than did the risk T allele (P<0.01), which implied rs10514611 was a potential functional SNP site.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, China.

ABSTRACT
Genes encoding IRF1 and IRF8 protein have been proposed as candidate tuberculosis susceptibility genes. In order to elucidate whether the IRF1 and IRF8 variants were associated with tuberculosis susceptibility, we conducted a case-control study consisting of 495 controls and 452 ethnically matched cases with tuberculosis in a Chinese population. Seven haplotype tagging single-nucleotide polymorphisms (tagSNPs) (rs2057656; rs2706381; rs2070724; rs2070721; rs2549008; rs2549007; rs2706386) from HapMap database were analyzed, which provided an almost complete coverage of the genetic variations in the IRF1 gene. Fifteen tagSNPs (rs12924316; rs182511; rs305080; rs2292980; rs925994; rs424971; rs16939967; rs11117415; rs4843860; rs9926411; rs8064189; rs12929551; rs10514611; rs1044873; rs6638) were observed in the IRF8 gene. All these tagSNPs were genotyped by SNPstream genotyping and SNaPshot typing. None of the seven tagSNPs was individually associated with tuberculosis in the IRF1 gene. In the IRF8 gene, interestingly, we found that three tagSNPs (rs925994 and rs11117415 located in the intron region; rs10514611 located in the 3'UTR) were associated with risk of tuberculosis after Bonferroni correction. Per allele OR was 1.75 (95% CI 1.35 ~ 2.27, P = 0.002), 4.75 (95% CI 2.16 ~ 10.43, P = 0.002) and 3.39 (95% CI 1.60 ~ 7.20, P = 0.015) respectively. Luciferase reporter gene assay showed that the construct that contained the non-risk allele C of rs10514611 showed significantly higher luciferase activity than did the risk T allele (P<0.01), which implied rs10514611 was a potential functional SNP site. Our results indicated that the IRF8 gene might participate in genetic susceptibility to tuberculosis in a Chinese population.

Show MeSH
Related in: MedlinePlus