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Cardiorenal Med. 2016 Aug;6(4):301-6. doi: 10.1159/000445754. Epub 2016 May 20.

Genetic Variants in Toll-Like Receptor 4 Gene and Their Association Analysis with Estimated Glomerular Filtration Rate in Mexican American Families.

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Division of Nephrology, Department of Medicine, University of Texas Health Science Center, San Antonio, Tex, USA; Department of Biochemistry, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
Department of Genetics, Texas Biomedical Research Institute, San Antonio, Tex, USA.
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, Tex., and Edinburg, Tex., USA.
Division of Nephrology, Department of Medicine, University of Texas Health Science Center, San Antonio, Tex, USA; South Texas Veterans Healthcare System, San Antonio, Tex, USA.



Toll-like receptor 4 (TLR4) is one of the regulators of the innate immune response. Genetic variations in TLR4 have been associated with inflammatory diseases, including type 2 diabetes. However, to our knowledge, there are no reports on the role of variations in TLR4 in chronic kidney disease susceptibility. The objective of this study is to determine whether the genetic variants in TLR4 are associated with the estimated glomerular filtration rate (eGFR), a measure of renal function.


To evaluate the association between TLR4 variants and eGFR, we used data obtained from 434 Mexican American participants from the San Antonio Family Diabetes/Gallbladder Study. GFR was estimated using the Modification of Diet in Renal Disease formula. The Asp(299)Gly (rs4986790) and Thr(399)Ile (rs4986791) variants of TLR4 were genotyped using the TaqMan assay. Association analyses between genotypes and eGFR were performed using the measured genotype approach.


Of the two genetic markers examined for association, only the Asp(299)Gly variant of TLR4 exhibited a nominally significant association with eGFR (p = 0.025) after accounting for the covariate effects of age and sex terms, diabetes, duration of diabetes, systolic blood pressure, body mass index, and antihypertensive treatment. Carriers of Gly299 had significantly decreased eGFR values. Although, the Thr(399)Ile variant failed to exhibit a statistically significant association with eGFR, the carriers of Ile399, however, showed a trend towards decrease in eGFR.


We show for the first time that Asp(299)Gly variants of TLR4 are associated with decrease in renal function in Mexican Americans.


Asp(299)Gly; Estimated glomerular filtration rate; Mexican Americans; Thr(399)Ile; Toll-like receptor 4; rs4986790; rs4986791

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