Evidence of potential interaction of chemokine genes in susceptibility to systemic sclerosis.
OBJECTIVE
To examine genetic polymorphisms in the chemokine pathway, and to assess their interactions in relation to susceptibility to systemic sclerosis (SSc).


METHODS
To identify the risk of SSc conferred by genetic polymorphisms in the chemokine pathway, 10 single-nucleotide polymorphisms (SNPs) from 8 candidate genes were studied in 99 patients with SSc and 198 age- and sex-matched controls in a Korean population. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism or sequence-specific primer methods. Genetic associations between each SNP and SSc risk, calculated as odds ratios with 95% confidence intervals, were estimated using chi-square tests. Haplotypes for the 2 polymorphisms in the gene CCL5 (RANTES) were constructed, and their associations with SSc were tested. Gene-gene interactions were investigated using a recently described novel method, and the results were confirmed by conditional logistic regression. Adjustment for multiple testing was based on Bonferroni correction.


RESULTS
There was significant evidence of gene-gene interaction between polymorphisms in the genes CXCL8 (interleukin-8) and CCL5, and both of these were associated with an increased risk of SSc. This SNP-SNP interaction was confirmed by 2 independent statistical methods. The associations remained significant after Bonferroni adjustment for multiple testing. No significant association between each individual SNP or haplotype and the risk of SSc was found.


CONCLUSIONS
Crosstalk between the 2 chemokines CXCL8 and CCL5 may contribute to the susceptibility to SSc.
Lee
Eun Bong
EB
Seoul National University, Seoul, Republic of Korea.
Zhao
Jinying
J
Kim
Jeong Yeon
JY
Xiong
Momiao
M
Song
Yeong Wook
YW
D018946:Chemokine CCL5; D018925:Chemokines / Q000235:genetics*; D019742:Chemokines, CC / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D007723:Korea; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D012595:Scleroderma, Systemic / Q000235:genetics*
C483024:CCL5 protein, human; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D016209:Interleukin-8