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A miRNA-492 binding-site polymorphism in BSG (basigin) confers risk to psoriasis in Central South Chinese population

Abstract

Psoriasis (PS; MIM#177900) is a chronic inflammatory immune-mediated skin disorder. Although the disease is believed to be caused by a combination of genetic, immunologic and environmental factors, its complete etiology has not been fully understood. Here, we focused on the BSG (MIM#109480), a member of the immunoglobulin superfamily expressed ubiquitously in circulating immune cell populations. We observed that the expression level of BSG in PBMCs was elevated in psoriasis patients. To understand the underlying mechanism for this change, we genotyped the rs8259 T>A SNP located in the 3′UTR of the BSG gene from 668 psoriasis patients and 1,143 healthy controls. The rs8259 T allele was associated with significantly decreased psoriasis susceptibility (OR = 0.758, 95% CI 0.638–0.901, p = 0.002). Interestingly, the rs8259 polymorphism was located in a seed region for miR-492 binding. The miR-492 was able to bind to the BSG 3′UTR sequence bearing the rs8259 T allele as assayed by luciferase reporter gene assay. The substitution of T with A abolished miR-492 binding. BSG protein expression in PBMCs from patients carrying the rs8259 AA genotype was significantly higher than in those from patients carrying the rs8259 TT genotype. Our study suggests that miR-492 may physiologically suppress BSG expression and the BSG rs8259 polymorphism is associated with decreased psoriasis susceptibility through affecting miR-492 binding.

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Abbreviations

BSG:

Basigin

SNP:

Single nucleotide polymorphism

UTR:

Untranslated region

HEK293T:

Human embryonic kidney-T

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Acknowledgments

We thank Prof. Yuanjian Li (School of Pharmaceutical Science, Central South University) with technical issues and suggestions as well as Hongfu Xie, Mingliang Chen, Wei Shi, Wu Zhu, Bo Deng, Huan Chen, Jianglin Zhang, Dan Jian, Jie Li (the Department of Dermatology in XiangYa Hospital, Central South University) for their help with collecting subjects. We thank Prof. Xuejun Zhang, Prof. Sen Yang (Anhui Medical University) Prof. Lunquan Sun (Center for Molecular Research, CSU) and Prof. Jiada Li (National Laboratory of Medical Genetics of China) for assistance. We thank National Laboratory of Medical Genetics of China for technical support. Contract grant sponsors: National Natural Science Foundation of China (Grant number: 81071290; 30872267; 30800990; 81072461); Program for Changjiang Scholars and Innovative Research Team in University; Program for New Century Excellent Talents in University (Grant number: NCET-07-0859); Aid program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province.

Conflict of interest

The authors have declared that no conflict of interest exists.

Author information

Correspondence to Xiao-Ping Chen or Xiang Chen.

Additional information

L.-S. Wu, F.-F. Li and L.-D. Sun contributed equally to this work.

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Wu, L., Li, F., Sun, L. et al. A miRNA-492 binding-site polymorphism in BSG (basigin) confers risk to psoriasis in Central South Chinese population. Hum Genet 130, 749–757 (2011). https://doi.org/10.1007/s00439-011-1026-5

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Keywords

  • Psoriasis
  • Psoriasis Patient
  • Single Nucleotide Polymorphism Rs8259
  • miRNA Binding Site
  • Psoriasis Susceptibility