Association of chemokine CXCL12-3'G801A polymorphism with systemic lupus erythematosus in a Han Chinese population.
CXCL12, also known as stromal cell-derived factor (SDF-1), is a CXC chemokine. Recent reports have shown that CXCL12 might play key roles in a murine model of lupus and in patients with systemic lupus erythematosus (SLE). A common variant at position 801 in 3'-untranslated region in CXCL12 gene (designated CXCL12-3'G801A) has been reported in association with autoimmune diseases, such as type 1 diabetes and systemic sclerosis. We investigated the influence of CXCL12-3'G801A polymorphism on susceptibility to SLE by genotyping this single nucleotide polymorphism in 422 SLE patients and 374 healthy controls. The frequency of G/G homozygote was observed in 60.0% of SLE patients and in 52.7% of healthy individuals (χ(2 )= 4.275, p = 0.039). Compared with patients with G/A and A/A genotype, SLE patients with G/G genotype were also more prone to developing photosensitivity (χ(2 )= 6.778, p = 0.034), renal damage (χ(2 )= 6.388, p = 0.041) and to producing antibodies against nucleosomes (χ(2 )= 8.341, p = 0.015). Moreover, the plasma level of CXCL12α was also significantly increased in patients with G/G homozygote than in healthy controls carrying the same genotype [(4067.0 ± 1092.3) pg/ml vs. (3278.5 ± 547.4) pg/ml, p = 0.002]. Our results suggest that polymorphism in CXCL12-3'G801A might be a genetic risk factor for developing SLE. The association of G/G homozygote with nephritis and skin damage developed in SLE patients might be due to its effects upon the production of auto-antibodies and CXCL12 protein.
Department of Rheumatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
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Wu
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Luo
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Wu
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Yang
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Long
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Liu
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Zhou
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Zeng
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Yang
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Yuan
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D054377:Chemokine CXCL12 / Q000235:genetics*; D002648:Child; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
D054377:Chemokine CXCL12