A replication study from Chinese supports association between lupus-risk allele in TNFSF4 and renal disorder.
A recent phenotypic association study of genetic susceptibility loci in SLE suggested that TNFSF4 gene might be useful to predict renal disorder in lupus patients. To replicate the association, two single-nucleotide polymorphisms (SNPs: rs2205960 and rs10489265) were genotyped in 814 SLE patients. Correlations between genotypes and TNFSF4 expression were determined. The stainings of TNFSF4 in renal biopsy specimens were checked by immunohistochemistry. The SNPs of TNFSF4 were associated with renal involvement in lupus patients from the Chinese population (P values for rs2205960 and rs10489265 were 0.014 and 0.005 in additive model, resp.). An association between risk genotypes and low C3 levels was also observed (P = 0.034). Functional prediction suggested that rs2205960 had a regulatory feature. The risk alleles seemingly correlated with lower TNFSF4 expression. Strong TNFSF4 expression was detected in lymph nodes and "apparently normal" paratumor renal biopsy but not in renal biopsies from lupus nephritis. In genome-wide expression data, TNFSF4 was also observed to be downregulated in LN in both glomeruli and tubulointerstitium from kidney biopsies. However, the associations were marginally significant. Our data firstly replicated the association of TNFSF4 with renal disorder in SLE patients in the Chinese population, which supported that TNFSF4 may act as a marker of lupus nephritis. The detailed mechanisms of its role in pathogenesis will still be further needed.
Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China.
Xu-jie
XJ
Zhou
Fa-juan
FJ
Cheng
Yuan-yuan
YY
Qi
Ming-hui
MH
Zhao
Hong
H
Zhang
D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008178:Lupus Erythematosus, Cutaneous / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008181:Lupus Nephritis / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D053278:OX40 Ligand / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D053278:OX40 Ligand; C089251:TNFSF4 protein, human