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Association of Arachidonate 12-Lipoxygenase Genotype Variation and Glycemic Control With Albuminuria in Type 2 Diabetes

Citation

Liu, Y and Freedman, BI and Burdon, KP and Langefeld, CD and Howard, T and Herrington, D and Goff Jr, DC and Bowden, DW and Wagenknecht, LE and Hedrick, CC and Rich, SS, Association of Arachidonate 12-Lipoxygenase Genotype Variation and Glycemic Control With Albuminuria in Type 2 Diabetes, American Journal of Kidney Diseases, 52, (2) pp. 242-250. ISSN 0272-6386 (2014) [Refereed Article]

DOI: doi:10.1053/j.ajkd.2007.12.033

Abstract

Background: Glycemic exposure activates 12-lipoxygenase (12LO) expression and formation of arachidonic acid-derived products. These products can induce cell hypertrophy, cell proliferation, and extracellular matrix deposition, potentially leading to diabetic nephropathy. Study Design: Cross-sectional study. Settings & Participants: 955 European-American siblings from 369 Diabetes Heart Study families. Participants were categorized as nondiabetic, diabetic with hemoglobin A1c level less than 6.5%, and diabetic with hemoglobin A1c level greater than 6.5% (uncontrolled type 2 diabetes mellitus). Predictor: Four haplotype-tagging variants in the arachidonate 12LO gene (ALOX12), glycemic control, and other covariates. Outcomes & Measurements: Albuminuria measured by means of urinary albumin-creatinine ratio (ACR). Results: Median ACR was 11.9 mg/g (interquartile range, 5.6 to 39.1). The overall test of the Arg261Gln genotypic association with ACR was significant (P = 0.009). Compared with 261Arg allele carriers, adjusted mean ACR was 42% greater in the 189 carriers of two 261Gln alleles (95% confidence interval, 10 to 83; P = 0.007). This association was confined to the group with uncontrolled type 2 diabetes mellitus (N = 623) with the greatest ACRs (P < 0.001). Adjustments for additional determinants of ACR yielded similar results. Limitations: Urine ACR was measured in duplicate on only a single occasion. This study was limited to European Americans. Conclusions: Consistent with animal and cellular studies, these results provide additional evidence of the importance of the 12LO pathway in the pathogenesis of human diabetic nephropathy.

Item Details

Item Type:Refereed Article
Keywords:albuminuria; ALOX12 gene; diabetic nephropathy; genetics; Lipoxygenase; type 2 diabetes mellitus
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Quantitative Genetics (incl. Disease and Trait Mapping Genetics)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Diabetes
Author:Burdon, KP (Associate Professor Kathryn Burdon)
ID Code:91055
Year Published:2014 (online first 2008)
Web of Science® Times Cited:9
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-05-06
Last Modified:2014-05-06
Downloads:0

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