Korean Journal of Nephrology 2002;21(1):137-144.

원저 : Monocyte Chemoattractant Protein - 1 ( MCP-1 ) 조절부위에 따른 유전자다형성이 MCP-1 발현 및 낭창성 신염에 미치는 영향 (Original articles : The Effects of Polymorphism in the MCP-1 Gene Regulatory Region on MCP-1 Expression and the Manifestation of Lupus Nephritis)

오윤규(Yoon Kyu Oh),한진석(Jin Suk Han),안규리(Cu Rie Ahn),이정은(Joung Eun Lee),김연수(Yon Su Kim),김성권(Suhng Gwon Kim),이정상(Jung Sang Lee),김현리(Hyun Lee Kim),양승희(Seung Hee Yang),오지은(Ji Eun Oh),윤형진(Hyung Jin Yoon)

Abstract

Background
: Monocyte chemoattractant protein- 1(MCP-1) plays an important role in progression of lupus nephritis.(LN) The genetic polymorphism in the regulatory region would influence clinical manifestations by controlling serum levels of MCP-1. Methods : We determined the genotypes of the MCP-1 gene, the secretion of MCP-1 by pheripheral blood monocytes(PBMCs) and transcription activity according to polymorphism on ELISA and luciferase assay. We also correlated serum MCP-1 level with proteinuria according to the genotypes to evaluate the clinical implication of genetic polymorphism in LN. Results : 10 patients with SLE(20%) were AA homozygous, 21(42%) GA heterozygous, and 18(38%) GG homozygous, which was similar with normal controls[AA 9(20%), GA 27(58%), GG 46(22%)](n= 46). By in-vitro stimulation of PBMCs using Phytohemagglutinin, differential expression of MCP-1 appeared according to the genotypes at -2518 position; PBMCs from AA homozygotes 22.37±0.07 ng/mL, GA 6.98±0.72 ng/mL, GG 5.48±0.22 ng/mL. In the luciferase assay, the gene construct with G at -2518 site showed decreased activity to 39% of that showed by A gene construct. In addition, After cells were treated with TNF-α(10 ng/mL), the transcription activity of A gene construct was approximately 3 fold greater than that of G gene construct. Levels of serum MCP-1 were significantly higher in patients with SLE(n=89) than normal controls(n=21)(418.17±935.30 pg/mL vs. 127.78±114.53 pg/mL, respectively; p<0.05). In contrast, there were no significant differences in serum MCP-1 levels between patients with LN, patients without LN and normal controls. Also, correlation between serum MCP-1 levels and proteinuria was not found(r=0.191, p>0.05). But, in patients with LN, levels of serum MCP-1 were significant higher in patients with AA genotype than those of GA genotyes and GG genotypes(p<0.01). Conclusion : MCP-1 gene polymorphism at regulatory region may be a considerable marker for LN and may modulate the level of protein expression. Our study could make it possible to screen high risk individuals, thus help us to develop a practical application of the molecular findings in clinical practice. (Korean J Nephrol 2002;21(1):137-144)