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Association of toll-like receptor 4 gene polymorphisms with primary membranous nephropathy in a high prevalence renal disease area in Taiwan

Shih-Yin Chen^a,b, Wen-Chi Chen^a,b, Yung-Hsiang Chen^b, Cheng-Hsu Chen^c, Yu-Chuen Huang^a,b, Po-Hsun Huang^d, Yi-Wen Lin^b, Huey-Yi Chen^a,b, Wen-Ling Liao^b, Fuu-Jen Tsai^a,b,*

 
ABSTRACT:     Membranous glomerulonephritis (MGN) is one of the most common causes of idiopathic nephrotic syndrome in adults. TLR4 gene polymorphisms have been reported to be associated with many inflammatory diseases. The objective of this study was to clarify the relationship between TLR4 gene polymorphisms and the pathogenesis of MGN. We recruited a cohort of 134 biopsy-diagnosed MGN patients and 263 healthy subjects that served as controls. Genotyping of TLR4 gene polymorphisms was performed using allele-specific polymerase chain reaction methods. We then analysed associations between TLR4 gene polymorphisms and clinical manifestations and pathogenesis of MGN. There was statistically significant difference of TLR4 gene rs10983755 A/G (p<0.001) and rs1927914 A/G (p<0.05) polymorphisms between controls and patients with MGN. The distributions of rs10759932 C/T and rs11536889 C/T polymorphisms were significantly different. A higher level of triglyceride was found in the non-GG group than in the GG group. The genotype of the non-AA group had a significantly higher ratio of proteinuria than that of the AA group. In addition, the distribution of haplotype frequencies of the TLR4 gene in 4 genetic variants revealed no statistical difference between normal patients and controls. The results demonstrated that patients with MGN have a different genotype distribution of the TLR4 gene from the normal controls. Our observations suggest that those polymorphisms contribute to the genetic background of MGN pathogenesis.

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* Corresponding author, E-mail: d0704@mail.cmuh.org.tw

Received 3 Feb 2010, Accepted 7 May 2010