title: Association of arachidonate 12-lipoxygenase genotype variation and glycemic control with albuminuria in type 2 diabetes.
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.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  955 European-American siblings from 369 Diabetes Heart Study families. Participants were categorized as nondiabetic, diabetic with hemoglobin A(1c) level less than 6.5%, and diabetic with hemoglobin A(1c) level greater than 6.5% (uncontrolled type 2 diabetes mellitus).
  
  
  METHODS
  Four haplotype-tagging variants in the arachidonate 12LO gene (ALOX12), glycemic control, and other covariates.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, UAS. yoliu@wfubmc.edu
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Timothy
authors.initials: T
authors.lastname: Howard
authors.forename: David
authors.initials: D
authors.lastname: Herrington
authors.forename: David C
authors.initials: DC
authors.lastname: Goff
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Wagenknecht
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Hedrick
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D044469:Racial Groups; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology
chemical_list: D001092:Arachidonate 12-Lipoxygenase; D001786:Blood Glucose; D004247:DNA; D006442:Glycated Hemoglobin