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


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.
Benjafield
A V
AV
Department of Physiology and Institute for Biomedical Research, the University of Sydney, Australia.
Glenn
C L
CL
Wang
X L
XL
Colagiuri
S
S
Morris
B J
BJ
D000368:Aged; D000419:Albuminuria; D000483:Alleles; D001315:Australia; D001794:Blood Pressure; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II; D014280:Triglycerides / Q000097:blood; D044465:White People
D002784:Cholesterol; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005819:Genetic Markers; D006442:Glycated Hemoglobin; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014280:Triglycerides; C415902:TNFRSF1B protein, human