TNFRSF1B in Genetic Predisposition to Clinical Neuropathy and Effect on HDL Cholesterol and Glycosylated Hemoglobin in Type 2 Diabetes
- Adam V. Benjafield, BMEDSC1,
- Cheryl L. Glenn, BMEDSC1,
- Xing Li Wang, MD, PHD245,
- Stephen Colagiuri, MB, BS, PHD3 and
- Brian J. Morris, PHD, DSC1
- 1Basic Clinical Genomics Laboratory, Department of Physiology and Institute for Biomedical Research, the University of Sydney, Sydney, Australia
- 2Cardiovascular Genetics Laboratory and the
- 3Department of Endocrinology, Prince of Wales Hospital, Sydney, Australia
- 4Centre for Thrombosis and Vascular Research, University of New South Wales, Sydney, Australia
- 5Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas
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; χ2 = 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.
- ANOVA, analysis of variance
- apoA-I, apolipoprotein A-I
- OR, odds ratio
- sTNF-R2, soluble tumor necrosis factor receptor 2
- TNF, tumor necrosis factor
- TNF-R2, tumor necrosis factor receptor 2
- UTR, untranslated region
Footnotes
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Address correspondence and reprint requests to Professor Brian J. Morris, Basic Clinical Genomics Laboratory, Department of Physiology and Institute for Biomedical Research, Building F13, The University of Sydney, Sydney, NSW 2006, Australia. E-mail: brianm{at}physiol.usyd.edu.au.
Received for publication 12 September 2000 and accepted in revised form 13 December 2000.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
