Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

Gender Specific Association of X-Linked TLR7 with Male SLE

Shen1,  N., Fu2,  Q., Deng1,  Y., Zhao2,  J., Qian1,  X. X., Kaufman3,  K M., Tang1,  Y J.

Ren Ji Hosp, Shanghai
Hanyang Univ
Seoul National Univ
Oklahoma Medical Res Fnd
Chang Gung Memorial Hosp, Taiwan
Univ of Tsukuba
Tokyo Women's Medical Univ
Ohio State Univ
Tan Tock Seng Hosp, Singapore


Duplicated Tlr7 promotes lupus-like disease in male BXSB-Yaa mice, prompting us to evaluate TLR7 in SLE patients especially in males.


SNP genotyping was conducted using the Illumina Infinium platform in the discovery panel, and Taqman or pyrosequencing in replication panels. Relative expression of TLR7 mRNA in PBMC was measured by RT-qPCR.


Fine-mapping the 23-kb TLR7 region using 11 SNPs in 1434 SLE cases of Eastern Asian (EA) descent vs. 1591 EA controls showed association of 2 TLR7 SNPs with SLE (rs5935436 in the promoter, p=1.8×10-3; rs3853839 in the 3'UTR, p=6.7×10-4). In this discovery panel, the association signal of the 3'UTR SNP was mainly found in Chinese (cases/controls; 563/522, p = 6.3×10-6) with a higher OR in males than females (OR = 5.6 vs. 1.5), but not detected in Koreans (845/1022). This association with SLE with a stronger male effect was replicated in both independent panels of Chinese (2133/2069, p = 1.8×10-5, OR = 3.1 vs. 1.3) and Japanese (560/913, p=0.007, OR = 3.5 vs. 1.2). In the combined analysis of 4127 cases and 4573 controls, the G allele of the 3'UTR SNP was associated with SLE (p = 2.4 ×10-12) exhibiting a higher OR in males than females (OR = 2.5 [1.7–3.5]) vs. 1.3 [1.2–1.4]). Healthy Chinese controls of either gender carrying only the risk G allele had significantly higher mRNA level of TLR7 in PBMC than those carrying allele C only, which was similarly found in female Chinese SLE patients, suggesting regulation of TLR7 expression by this SNP or its linked variants.


Association between the X-linked TLR7 SNP and SLE with a stronger male effect was identified in EA and replicated in independent Chinese and Japanese panels. This risk allele may confer elevated expression of the RNA-binding TLR7, predisposing to the development of SLE, especially in male Chinese or Japanese.

Table. Association of rs3853839 with SLE in EA population.

    G Allele Frequency  
EthnicityPanelsSexCase/ControlCaseControlPOR (95%CI)
Eastern Asian*DiscoveryM126/2290.830.730.041.8 [1.0–3.1]
  F1308/13620.790.763.0E–031.2 [1.1–1.4]
  All1434/15910.800.766.7E–041.2 [1.1–1.4]
ChineseDiscoveryM61/1450.930.727.0E–045.6 [1.9–16.7]
  F502/3770.830.762.0E–041.5 [1.2–2.0]
  All563/5220.830.756.3E–061.7 [1.3–2.1]
 ReplicationM181/8190.920.808.3E–053.1 [1.7–5.6]
  F1952/12500.830.804.4E–041.3 [1.1–1.4]
  All2133/20690.840.801.8E–051.3 [1.2–1.5]
 Total ChineseM242/9640.930.797.5E–073.5 [2.0–5.8]
  F2457/16270.830.799.8E–071.3 [1.2–1.5]
  All2696/25910.840.792.9E–091.4 [1.2–1.5]
JapaneseReplicationM36/3900.890.690.013.5 [1.2–10.2]
  F524/5230.750.710.041.2 [1.0–1.5]
  All560/9130.750.707.0E–031.3 [1.1–1.5]
Eastern Asian*CombinedM343/14380.890.764.2E–072.5 [1.7–3.5]
  F3784/31350.810.773.0E–091.3 [1.2–1.4]
* : comprised of subjects of Chinese, Korean or Japanese descent

To cite this abstract, please use the following information:
Shen, N., Fu, Q., Deng, Y., Zhao, J., Qian, X. X., Kaufman, K M., et al; Gender Specific Association of X-Linked TLR7 with Male SLE [abstract]. Arthritis Rheum 2009;60 Suppl 10 :643
DOI: 10.1002/art.25723

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