TNFRSF1B in genetic predisposition to clinical neuropathy and effect on HDL cholesterol and glycosylated hemoglobin in type 2 diabetes

Diabetes Care. 2001 Apr;24(4):753-7. doi: 10.2337/diacare.24.4.753.

Abstract

Objective: Genetic variation in the tumor necrosis factor (TNF) receptor 2 gene (TNFRSF1B) has shown association with insulin resistance in type 2 diabetes, hypercholesterolemia, coronary artery disease, and essential hypertension. Here we tested the TNFRSF1B marker used in the latter studies in type 2 diabetes patients.

Research design and methods: A case-control study of a microsatellite marker with five alleles (CA13- CA17) in intron 4 of TNFRSF1B was performed in 357 well-characterized white patients and 183 healthy control subjects.

Results: The CA16 allele was associated with clinical neuropathy (frequency = 27% in 69 patients with the condition versus 16% in 230 subjects without the condition; chi2 = 9.0, P = 0.011; odds ratio = 2.1 [95% CI 1.2-3.8]). No association was seen with other complications or diabetes itself. The CA16 allele tracked with elevation plasma HDL cholesterol (1.3 +/- 0.2, 1.2 +/- 0.4, and 1.1 +/- 0.2 for CA16/CA16, CA16/-, and -/-, respectively; n = 9, 110, and 218, respectively; P = 0.009) and reduction in plasma glycosylated hemoglobin (6.6 +/- 0.3, 8.3 +/- 0.2, and 8.1 +/- 0.1 for CA16/CA16, CA16/-, and -/-, respectively; n = 9, 102, 205, respectively; P = 0.007) Significance remained after Bonferroni correction for multiple testing.

Conclusions: Genetic variation in or near TNFRSF1B may predispose clinical neuropathy, reduced glycosylated hemoglobin, and increased HDL cholesterol in type 2 diabetes patients. The latter could be part of a protective response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria
  • Alleles
  • Australia
  • Blood Pressure
  • Case-Control Studies
  • Cholesterol / blood
  • Cholesterol, HDL / blood*
  • Cholesterol, LDL / blood
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Neuropathies / blood
  • Diabetic Neuropathies / genetics*
  • Diabetic Neuropathies / physiopathology
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Glycated Hemoglobin / analysis*
  • Humans
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / genetics*
  • Receptors, Tumor Necrosis Factor, Type II
  • Triglycerides / blood
  • White People

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Genetic Markers
  • Glycated Hemoglobin A
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type II
  • TNFRSF1B protein, human
  • Triglycerides
  • Cholesterol