Association between p.Leu54Met Polymorphism at the Paraoxonase-1 Gene and Plantar Fascia Thickness in Young Subjects with Type 1 Diabetes
- Patricia H Gallego, MD M.Sc (PatricG4{at}chw.edu.au)1,
- Maria E Craig, MBBS PhD FRACP1,,2,,3,
- Anthony C Duffin, PhD1,
- Bruce Bennetts, PhD FHGSA4,
- Alicia J Jenkins, MBBS MD FRACP FRCP5,
- Sabine Hofer, MD6,
- Albert Lam, MD FRACR7 and
- Kim C Donaghue, MBBS PhD FRACP1,,2
- 1Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, NSW Australia
- 2Discipline of Paediatrics and Child Health, University of Sydney
- 3School of Women's and Children's Health, University of New South Wales
- 4Department of Molecular Genetics, The Children's Hospital at Westmead, NSW Australia
- 5University of Melbourne, Department of Medicine (St. Vincent's), Melbourne, Australia
- 6Department of Paediatrics, Medical University of Innsbruck, Austria
- 7Department of Radiology, The Children's Hospital at Westmead, NSW Australia
Abstract
Objective: In type 1 diabetes, plantar fascia, a collagen-rich tissue, is susceptible to glycation and oxidation. Paraoxonase-1 (PON1) is an HDL-bound anti-oxidant enzyme. PON1 polymorphisms have been associated with macro and microvascular complication susceptibility. We investigated the relationship between plantar fascia thickness (PFT) and PON1 gene variants: p.Leu54Met, p.Gln192Arg and c.-107C>T in type 1 diabetes.
Research Design And Methods: Cross-sectional study of 331 adolescents with type 1 diabetes (162 M; 169 F). PFT was assessed by ultrasound; PON1 genotyping by PCR and restriction fragment length polymorphism (RFLP); serum PON1 activity by rates of hydrolysis of paraoxon and phenylacetate.
Results Median [interquartile range] age was 15.4 yrs [13.5 – 17.3] and diabetes duration was 7.6 yrs [ 4.9 – 10.6] . The distribution of p.Leu54Met genotypes was LL 135 (40.8%); ML 149 (45%) and MM 47 (14.2%). PFT was abnormal (>1.7mm) in 159 (48%). In multivariate analysis, predictors of abnormal PFT were ML/LL vs MM p.Leu54Met polymorphism (OR, [95% CI] 3.84 [1.49 – 9.82], p=0.005; BMI (percentile) 1.02, [1.01 – 1.03], p=0.007 and SBP (percentile) 1.01, [1.00 – 1.02], p=0.03; male gender 3.29, [1.98 – 5.46], p<0.001.
Conclusions Thickening of the plantar aponeurosis occurs predominantly in overweight and male adolescents with type 1 diabetes. The MM genotype at PON1 p.Leu54Met is associated with reduced risk of abnormal PFT.
Footnotes
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- Received November 25, 2007.
- Accepted May 2, 2008.
- Copyright © American Diabetes Association
