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Expression analysis ofETS1gene in peripheral blood mononuclear cells with systemic lupus erythematosus by real-time reverse transcription PCR

LI, Yun; SUN, Liang-dan; LU, Wen-sheng; HU, Wen-long; GAO, Jin-ping; CHENG, Yi-lin; YU, Ze-ying; YAO, Sha; HE, Cai-feng; LIU, Jian-lan; CUI, Yong; YANG, Sen

doi: 10.3760/cma.j.issn.0366-6999.2010.16.025
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Institute of Dermatology & Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230032, China (Li Y, Sun LD, Lu WS, Hu WL, Gao JP, Cheng YL, Yu XY, Yao S, He CF, Liu JL, Cui Y and Yang S)

Key Laboratory of Dermatology, Ministry of Education, Hefei, Anhui 230032, China (Li Y, Sun LD, Lu WS, Hu WL, Gao JP, Cheng YL, Yu XY, Yao S, He CF, Liu JL, Cui Y and Yang S)

Correspondence to: Dr. CUI Yong, Institute of Dermatology & Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road, Hefei, Anhui 230032, China (Email: wuhucuiyong@vip.163.com) This work was supported by grants from the General Program of National Natural Science Foundation of China (No. 30972727) and the Foundation of the Excellent Young Scientist of Anhui Province (No. 10040606Y10).

(Received March 31, 2010) Edited by GUO Li-shao

To the editor: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance.1 In recent years, genome-wide association studies (GWAS) had further provided novel insights into the genetics background of SLE by identifying multiple susceptibility genes in different ethnic populations.2 Single-nucleotide polymorphisms (SNPs) in E26 transformation-specific-1 (ETS1) gene has been shown to be associated with SLE,3 implicating by one highly associated SNPs6590330 (OR=1.37, 95% CI: 1.29–1.45, P=1.77×10-25). ETS1 may play a role both in innate and adaptive immune response,4 but its expression level in SLE has been poorly understood. Our current study aimed to assess the association of ETS1 gene expression level with SLE.

A total of 61 unrelated Chinese Hans SLE patients (with the mean age of 34.9 years) were recruited consecutively from the outpatients at the Department of Dermatology, the First Affiliated-Hospital, Anhui Medical University. All patients fulfilled the diagnostic criteria of the American College of Rheumatology (ACR). The healthy controls were comprised of 67 disease-free unrelated individuals, age-, sex-, and ethnicity-matched with the patients from the same areas. We used the same questionnaire to collect information from patients and controls. Peripheral blood from cases and controls were obtained with informed consent and all protocols were approved by the ethical committee of the Anhui Medical University.

The range of SLE Disease Activity Index (SLEDAI) was from 0 to 26, and the mean value was 9.38. The butterfly erythema and arthritis is the major indicator of morbidity of in SLE, which were found in 37 of 61 patients. The hematological disease was the commonest manifestation, which was found in 27 of 61 patients. The lupus nephritis was observed in 25 patients. The dental ulcer, photesthesis, serositis, and central nervous system disease were found in 14, 10, 2, and 0 patients, respectively.

Fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to examine the expression of ETS1 mRNA in peripheral blood mononuclear cells (PBMCs) and Sequenom MassArray system was used to genotype single nucleotide polymorphism (rs6590330) in 61 case of SLE and 67 normal controls. The SPSS10.0 software was used for statistical analysis. The results showed that the ETS1 mRNA expression levels of SLE patients (0.3240±0.1137) was significantly lower than that of healthy controls (0.4128±0.151, P <0.001, Figure). Through stratified analysis, we measured the result of expression which showed no significance difference (P >0.05) between SNPrs6590330.

In this study, we found that the significant difference of expression level ETS1 in SLE patients compared to healthy controls among the Chinese Han Populations. Difference of expression level of ETS1 has not been described in relation to SLE before. This study showed that ETS1 mRNA level in PBMCs of SLE was lower. The pathogenesis of SLE is complex, with both genetic and nongenetic factors contributing to the development of the disease. The genetic susceptibility basis of SLE has been largely unknown, and our understanding of the disease mechanism is limited.

Figure.

Figure.

ETS1 plays an important role in embryonic development including immune cells. Absence of ETS1 leads to abnormal B lymphocyte differentiation, resulting in increased numbers of immunoglobulin (Ig) M-secreting plasma cells.5 The decreased expression of ETS1 gene may contribute to SLE pathogenesis through regulating T cell activation. Immune homeostasis is maintained by multiple immune regulation genes that cannot compensate for each other. Breakdown of immune homeostasis caused by dysfunction of these genes contributes to the pathogenesis of SLE. Hyperactivation of autoreactive T cell is a one of hallmarks of SLE.

In summary, our data suggest that ETS1 may play a role in the pathogenesis in SLE patients, although the exact mechanisms will require further investigation.

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Acknowledgements:

We are most grateful to all the members who have so willingly participated in this study, which made this study possible.

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REFERENCES

1. D′Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet 2007; 9561: 587-596.
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3. Han JW, Zheng HF, Cui Y, Sun LD, Ye DQ, Hu Z, et al. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet 2009; 11: 1234-1237.
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