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Diabetes Care Publish Ahead of Print published online ahead of print May 9, 2008
DOI: 10.2337/dc07-2236

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Original Research

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.Sc1, 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

PatricG4{at}chw.edu.au

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.


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