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Genetic variation in thioredoxin interacting protein (TXNIP) is associated with hypertriglyceridaemia and blood pressure in diabetes mellitus
Author(s) -
Van Greevenbroek M. M. J.,
Vermeulen V. M. MJ.,
Feskens E. J. M.,
Evelo C. T.,
Kruijshoop M.,
Hoebee B.,
Van Der Kallen C. J. H.,
De Bruin T. W. A.
Publication year - 2007
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2007.02109.x
Subject(s) - txnip , thioredoxin interacting protein , medicine , endocrinology , diabetes mellitus , type 2 diabetes mellitus , type 2 diabetes , single nucleotide polymorphism , hypertriglyceridemia , triglyceride , prediabetes , snp , allele , biology , genotype , gene , genetics , cholesterol , thioredoxin , oxidative stress
Aims Thioredoxin interacting protein (TXNIP) is an attractive candidate gene for diabetes or diabetic dyslipidaemia, since TXNIP is the strongest glucose‐responsive gene in pancreatic B‐cells, TXNIP deficiency in a mouse model is associated with hyperlipidaemia and TXNIP is located in the 1q21‐1q23 chromosomal Type 2 diabetes mellitus (DM) locus. We set out to investigate whether metabolic effects of TXNIP that were previously reported in a murine model are also relevant in human Type 2 DM. Methods The frequency distribution of a 3′ UTR single nucleotide polymorphism (SNP) in TXNIP was investigated in subjects with normal glucose tolerance (NGT; n = 379), impaired glucose tolerance (IGT; n = 228) and Type 2 DM ( n = 230). Metabolic data were used to determine the effect of this SNP on parameters associated with lipid and glucose metabolism. Results The frequency of the TXNIP variation did not differ between groups, but within the group of diabetic subjects, carriers of the TXNIP‐T variant had 1.6‐fold higher triglyceride concentrations ( P = 0.015; n = 136) and a 5.5‐mmHg higher diastolic blood pressure ( P = 0.02; n = 212) than homozygous carriers of the common C‐allele, whereas in non‐diabetic subjects fasting glucose was 0.26 mmol/l lower ( P = 0.002; n = 478) in carriers of the T‐allele. Moreover, a significant interaction between plasma glucose concentrations and TXNIP polymorphism on plasma triglycerides was observed ( P = 0.012; n = 544). Conclusion This is the first report to implicate TXNIP in a human disorder of energy metabolism, Type 2 diabetes. The effect of TXNIP on triglycerides is influenced by plasma glucose concentrations, suggesting that the biological relevance of TXNIP variations may be particularly relevant in recurrent episodes of hyperglycaemia.