Limits...
Genetic association study of TNFAIP3, IFIH1, IRF5 polymorphisms with polymyositis/dermatomyositis in Chinese Han population.

Chen S, Wang Q, Wu Z, Li Y, Li P, Sun F, Zheng W, Wu Q, Wu C, Deng C, Zhang F, Li Y - PLoS ONE (2014)

Bottom Line: And rs2230926 and rs5029939 were significantly associated with interstitial lung disease (ILD) in PM/DM and PM patients (P(c) = 0.04 and P(c) = 0.016; P(c) = 0.02 and P(c) = 0.03, respectively).In addition, rs4728142 allele and genotype had significant association with PM/DM patients (P(c) = 0.026 and P(c) = 0.048, respectively).This was the first study to reveal TNFAIP3 and IRF5 polymorphisms were associated with PM/DM patients or these patients with ILD, indicating that TNFAIP3 and IRF5 might be the susceptibility gene for PM/DM patients in Chinese Han population.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

ABSTRACT

Background: Single-nucleotide polymorphisms (SNPs) in the TNFAIP3, IFIH1, and IRF5 genes have been associated with several auto-inflammation diseases, while the susceptibility between these genes and idiopathic inflammatory myopathies (IIMs) were not reported. This study aimed to investigate whether TNFAIP3, IFIH1, and IRF5 gene polymorphisms confer susceptibility for the IIMs in Chinese Han population.

Methods: A large case-control study of Chinese subjects with polymyositis (PM) (n = 298) and dermatomyositis (DM) (n = 530) was accomplished. 968 healthy and ethnically matched controls were available for comparison. Six SNPs in the TNFAIP3 region (rs2230926 and rs5029939), the IFIH1 gene (rs1990760 and rs3747517) and the IRF5 region (rs4728142 and rs729302) were assessed and genotyped using the Sequenom MassArray iPLEX platform.

Results: Our study indicated a strong allele association was observed in PM/DM and PM patients for rs2230926 (OR: 1.61, 95%CI: 1.20-2.16, P(c) = 7.5×10(-3); OR: 1.88, 95%CI: 1.30-2.74, P(c) = 4.0×10(-3), respectively) and rs5029939 (OR: 1.64, 95%CI: 1.21-2.21, P(c) = 6.0×10(-3); OR: 1.88, 95%CI: 1.28-2.76, P(c) = 5.5×10(-3), respectively). And rs2230926 and rs5029939 were significantly associated with interstitial lung disease (ILD) in PM/DM and PM patients (P(c) = 0.04 and P(c) = 0.016; P(c) = 0.02 and P(c) = 0.03, respectively). In addition, rs4728142 allele and genotype had significant association with PM/DM patients (P(c) = 0.026 and P(c) = 0.048, respectively). Further analysis with three logistic regression genetic models revealed statistically significant difference in the genotypic distribution in the PM/DM, PM or DM patients when the additive and dominant models were used.

Conclusions: This was the first study to reveal TNFAIP3 and IRF5 polymorphisms were associated with PM/DM patients or these patients with ILD, indicating that TNFAIP3 and IRF5 might be the susceptibility gene for PM/DM patients in Chinese Han population.

Show MeSH

Related in: MedlinePlus

Linkage disequilibrium (LD) analysis of the SNPs in the TNFAIP3 gene region.The LD plots were generated by Haploview software v4.2 and data from our study were similar to that from the HapMap CHB population. The number (divided by 100) in the small square represents r2 value and ranges from 0 to 1. The two SNPs (rs2230926 and rs5029939) in TNFAIP3 reside in an LD block. (A): The data from HapMap CHB. B: The data analysis between DM patients and healthy controls from our study. C: The data analysis between PM patients and healthy controls from our study. D: The data analysis between PM/DM patients and healthy controls from our study.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4206287&req=5

pone-0110044-g001: Linkage disequilibrium (LD) analysis of the SNPs in the TNFAIP3 gene region.The LD plots were generated by Haploview software v4.2 and data from our study were similar to that from the HapMap CHB population. The number (divided by 100) in the small square represents r2 value and ranges from 0 to 1. The two SNPs (rs2230926 and rs5029939) in TNFAIP3 reside in an LD block. (A): The data from HapMap CHB. B: The data analysis between DM patients and healthy controls from our study. C: The data analysis between PM patients and healthy controls from our study. D: The data analysis between PM/DM patients and healthy controls from our study.

Mentions: We used Haploview software to further analyze the distributions of the haplotypes in the TNFAIP3 SNPs between patients and healthy controls. The results from the LD analysis of the SNPs (rs2230926, rs5029939) in our study and the data from the HapMap CHB population were shown in Table 5 and Fig. 1. Data from HapMap CHB and the present study illustrated no significant differences. And strong LD association existed between rs2230926 and rs5029939 (r2 = 1). The CT haplotype (rs2230926 C–rs5029939 T) had a lower frequency between DM, PM or PM/DM patients and controls (Pc = 0.04, Pc = 2.5×10−3 and Pc = 2.0×10−3, respectively)(Table 5).


Genetic association study of TNFAIP3, IFIH1, IRF5 polymorphisms with polymyositis/dermatomyositis in Chinese Han population.

Chen S, Wang Q, Wu Z, Li Y, Li P, Sun F, Zheng W, Wu Q, Wu C, Deng C, Zhang F, Li Y - PLoS ONE (2014)

Linkage disequilibrium (LD) analysis of the SNPs in the TNFAIP3 gene region.The LD plots were generated by Haploview software v4.2 and data from our study were similar to that from the HapMap CHB population. The number (divided by 100) in the small square represents r2 value and ranges from 0 to 1. The two SNPs (rs2230926 and rs5029939) in TNFAIP3 reside in an LD block. (A): The data from HapMap CHB. B: The data analysis between DM patients and healthy controls from our study. C: The data analysis between PM patients and healthy controls from our study. D: The data analysis between PM/DM patients and healthy controls from our study.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4206287&req=5

pone-0110044-g001: Linkage disequilibrium (LD) analysis of the SNPs in the TNFAIP3 gene region.The LD plots were generated by Haploview software v4.2 and data from our study were similar to that from the HapMap CHB population. The number (divided by 100) in the small square represents r2 value and ranges from 0 to 1. The two SNPs (rs2230926 and rs5029939) in TNFAIP3 reside in an LD block. (A): The data from HapMap CHB. B: The data analysis between DM patients and healthy controls from our study. C: The data analysis between PM patients and healthy controls from our study. D: The data analysis between PM/DM patients and healthy controls from our study.
Mentions: We used Haploview software to further analyze the distributions of the haplotypes in the TNFAIP3 SNPs between patients and healthy controls. The results from the LD analysis of the SNPs (rs2230926, rs5029939) in our study and the data from the HapMap CHB population were shown in Table 5 and Fig. 1. Data from HapMap CHB and the present study illustrated no significant differences. And strong LD association existed between rs2230926 and rs5029939 (r2 = 1). The CT haplotype (rs2230926 C–rs5029939 T) had a lower frequency between DM, PM or PM/DM patients and controls (Pc = 0.04, Pc = 2.5×10−3 and Pc = 2.0×10−3, respectively)(Table 5).

Bottom Line: And rs2230926 and rs5029939 were significantly associated with interstitial lung disease (ILD) in PM/DM and PM patients (P(c) = 0.04 and P(c) = 0.016; P(c) = 0.02 and P(c) = 0.03, respectively).In addition, rs4728142 allele and genotype had significant association with PM/DM patients (P(c) = 0.026 and P(c) = 0.048, respectively).This was the first study to reveal TNFAIP3 and IRF5 polymorphisms were associated with PM/DM patients or these patients with ILD, indicating that TNFAIP3 and IRF5 might be the susceptibility gene for PM/DM patients in Chinese Han population.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

ABSTRACT

Background: Single-nucleotide polymorphisms (SNPs) in the TNFAIP3, IFIH1, and IRF5 genes have been associated with several auto-inflammation diseases, while the susceptibility between these genes and idiopathic inflammatory myopathies (IIMs) were not reported. This study aimed to investigate whether TNFAIP3, IFIH1, and IRF5 gene polymorphisms confer susceptibility for the IIMs in Chinese Han population.

Methods: A large case-control study of Chinese subjects with polymyositis (PM) (n = 298) and dermatomyositis (DM) (n = 530) was accomplished. 968 healthy and ethnically matched controls were available for comparison. Six SNPs in the TNFAIP3 region (rs2230926 and rs5029939), the IFIH1 gene (rs1990760 and rs3747517) and the IRF5 region (rs4728142 and rs729302) were assessed and genotyped using the Sequenom MassArray iPLEX platform.

Results: Our study indicated a strong allele association was observed in PM/DM and PM patients for rs2230926 (OR: 1.61, 95%CI: 1.20-2.16, P(c) = 7.5×10(-3); OR: 1.88, 95%CI: 1.30-2.74, P(c) = 4.0×10(-3), respectively) and rs5029939 (OR: 1.64, 95%CI: 1.21-2.21, P(c) = 6.0×10(-3); OR: 1.88, 95%CI: 1.28-2.76, P(c) = 5.5×10(-3), respectively). And rs2230926 and rs5029939 were significantly associated with interstitial lung disease (ILD) in PM/DM and PM patients (P(c) = 0.04 and P(c) = 0.016; P(c) = 0.02 and P(c) = 0.03, respectively). In addition, rs4728142 allele and genotype had significant association with PM/DM patients (P(c) = 0.026 and P(c) = 0.048, respectively). Further analysis with three logistic regression genetic models revealed statistically significant difference in the genotypic distribution in the PM/DM, PM or DM patients when the additive and dominant models were used.

Conclusions: This was the first study to reveal TNFAIP3 and IRF5 polymorphisms were associated with PM/DM patients or these patients with ILD, indicating that TNFAIP3 and IRF5 might be the susceptibility gene for PM/DM patients in Chinese Han population.

Show MeSH
Related in: MedlinePlus