Variations in the TNFα gene and their interactions with the IL4R and IL10 genes in relation to hand osteoarthritis

BMC Musculoskeletal Disorders

Ari Hirvonen¹  Päivi Leino-Arjas¹  Tapio Vehmas¹  Svetlana Solovieva¹  Satu Hämäläinen¹ 

[1] Finnish Institute of Occupational Health, Centre of Expertise for Health and Work Ability, Topeliuksenkatu 41 a A, FI-00250 Helsinki, Finland

关键词: Inflammation;    Hand osteoarthritis;    Individual susceptibility;    Gene polymorphism;    Tumor necrosis factor alpha;   

Others  :  1122083
DOI  :  10.1186/1471-2474-15-311

 received in 2014-05-10, accepted in 2014-09-19,  发布年份 2014

【 摘 要 】

Background

The development of osteoarthritis (OA) involves inflammation, but the evidence for participation of genes propagating or inhibiting inflammation in the OA process is inconsistent. We investigated the associations of common variants in the TNFα gene, and their interactions with other cytokine genes, with hand OA among Finnish women.

Methods

This cross-sectional study was based on bilateral hand radiographs of 542 female dentists and teachers which were classified according to the presence of OA (radiographic K-L score ≥ 2 in ≥ 3 joints) using reference images. The genotypes were determined by PCR-based methods. The degree of pairwise linkage disequilibrium (LD) and haplotypes were constructed and analyzed by the SNPStats software. The associations between four TNFα SNPs and hand OA were tested using logistic regression adjusting for age, occupation, and BMI, and fitting a log-additive model of inheritance. Gene-gene interactions of TNFα SNPs with IL4R and IL10 SNPs were examined by stratified logistic regression analyses. Possible interactions of the TNFα SNPs with variants in the previously reported IL1β and IL6 genes in influencing hand OA were also explored.

Results

Two TNFα polymorphisms (“-1031” and “-863”) were associated with hand OA (OR = 1.45, 95% CI 1.01-2.07 and 1.55, 1.06-2.25, respectively). These associations retained when adjusting further for IL1β “3954” and IL6 “174”. The TNFα G-A-G haplotype was associated with an increased risk of hand OA (1.61, 1.10-2.37, p = 0.01). Interactions were observed between TNFα “-1031” and IL4R Ser503Pro, TNFα “-1031” and IL10 “-1082”, and TNFα “-863” and IL10 “-1082” SNPs with regard to hand OA (p = 0.012, p = 0.0068, and p = 0.02, respectively). The carriage of the TNFα “-1031” minor allele doubled the risk (2.01, 1.26 - 3.22) only in women with the IL4R Ser/Ser genotype. Similarly, the TNFα “-1031” and “-863” minor alleles were associated with an increased risk of hand OA only in IL10 G/G or A/A homozygotes (2.54, 1.45-4.47 and 2.60, 1.46-4.62, respectively) but not in heterozygotes (G/A).

Conclusions

Our results suggest that the TNFα gene variants play a role in the etiology of hand OA. In addition, the findings are suggestive of a gene-gene interaction of the TNFα with IL4R and IL10 genes.

【 授权许可】

   
2014 Hämäläinen et al.; licensee BioMed Central Ltd.

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