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120 ASSOCIATION OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN −493G/T POLYMORPHISM WITH LIPID METABOLISM AND MICROVASCULAR COMPLICATIONS IN TYPE 2 DIABETIC PATIENTS.
  1. B. Ershoff1,
  2. V. Durlach2,
  3. A. Durlach3,
  4. I. Movesayan4,
  5. E. Socquard2,
  6. C. Clavel3,
  7. P. Nazeyrollas2,
  8. M. Malloy4,
  9. C. Pullinger4,5,
  10. J. Kane4,6,
  11. B. Aouizerat5,6
  1. 1School of Medicine, University of California, San Francisco, San Francisco, CA
  2. 2Service d'Endocrinologie, Hôpital Robert Debré, Centre Hospitalo-Universitaire, Reims, France
  3. 3Laboratoire Pol Bouin, Hôpital Maison Blanche, Centre Hospitalo-Universitaire, Reims, France
  4. 4Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA
  5. 5Department of Physiological Nursing, University of California, San Francisco, San Francisco, CA
  6. 6Institute for Human Genetics, University of California, San Francisco, San Francisco, CA.

Abstract

Background Type 2 diabetes (T2D) affects over 15 million Americans, and the prevalence is rising precipitously. T2D patients are at risk for atherosclerosis and microvascular complications; identifying those at risk can lead to improved outcomes. Risk for complications due to dyslipidemia is modulated by genetic factors. Common variations in the microsomal triglyceride transfer protein (MTP −493G/T) and apolipoprotein B (apoB insertion/deletion [In/Del]) genes may modulate the risk for diabetic complications through their impact on lipid metabolism.

Methods As part of a longitudinal case-control study of T2D in a French population (401 cases, 113 controls, mean age 59.5 years at baseline, and 4.2-year mean follow-up) we examined the relationship between MTP −493G/T, apoB In/Del, lipoprotein parameters, and the prevalence of diabetic complications.

Results After adjusting for relevant covariates, MTP −493G/T was associated with T2D (p = .032), lower apoB concentrations (p = .024), triglycerides (p = .047), total cholesterol (p = .049), body mass index (p = .006), and creatinine levels (p = .007). Given the biochemical interaction of apoB and MTP proteins in the assembly of triglyceride-rich lipoproteins, we tested for their genetic interaction as a predictor of apoB concentration; T2D individuals with MTP T/T and apoB In/In had the highest apoB concentrations (p = .05). MTP −493G/T was associated with nephropathy at follow-up (p = .048), with G-allele homozygotes more likely to have nephropathy than T-allele carriers (odds ratio = 1.621, 95% confidence interval 1.004, 2.616).

Conclusion MTP −493G/T is associated with T2D and impacts lipoprotein parameters associated with complications in T2D. Importantly, we contribute novel evidence that lipoprotein metabolism genes are risk factors for diabetic complications.

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