The Asp727Glu polymorphism in the TSH receptor is associated with insulin resistance in healthy elderly men
Robin P. Peeters, Wendy M. Van Der Deure, Annewieke W. Van Den Beld, Hans Van Toor, Steven W. J. Lamberts, Joop A. M. J. L. Janssen, André G. Uitterlinden,
Theo J. Visser,
André G. Uitterlinden
Departments of Internal Medicine,
Clinical Chemistry, and
Epidemiology and Biostatistics, Erasmus University Medical Centre, Rotterdam, The Netherlands
Search for more papers by this authorRobin P. Peeters, Wendy M. Van Der Deure, Annewieke W. Van Den Beld, Hans Van Toor, Steven W. J. Lamberts, Joop A. M. J. L. Janssen, André G. Uitterlinden,
Theo J. Visser,
André G. Uitterlinden
Departments of Internal Medicine,
Clinical Chemistry, and
Epidemiology and Biostatistics, Erasmus University Medical Centre, Rotterdam, The Netherlands
Search for more papers by this author Robin P. Peeters, Department of Internal Medicine, Room Ee 502, Erasmus University Medical Centre, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. Tel.: +31 10 4635463; Fax: +31 10 4635430; E-mail: [email protected]
Summary
Background Variations in thyroid function within the normal range are associated with differences in metabolism and body composition. For instance, TSH is positively associated with body mass index (BMI). This could be due to alterations in thyroid hormone activity, or to direct effects of TSH, as the TSH receptor (TSHR) is also expressed in adipose tissue. The TSHR-Asp727Glu polymorphism is associated with lower serum TSH levels in vivo. In this study, we analysed whether serum thyroid parameters and the TSHR-Asp727Glu polymorphism were associated with glucose metabolism and insulin resistance. In addition, we analysed the Thr92Ala polymorphism in the type 2 deiodinase (D2), which was recently associated with insulin resistance.
Methods Genotypes were determined in a population of 349 elderly men (age 77·7 ± 3·5 years), for whom serum thyroid parameters and data on insulin resistance, such as fasting blood glucose, serum insulin and homeostasis model assessment (HOMA) values, were available.
Results In nondiabetic, euthyroid subjects, TSH was positively associated with leptin levels, whereas FT4 and rT3 were significantly negatively correlated with insulin and HOMA. Carriers of the TSHR-Glu727 allele had a significantly higher glucose (P = 0·01), insulin (P = 0·001), glycated haemoglobin (HbA1c) (P = 0·002), HOMA (P = 0·001) and leptin (P = 0·008). The D2-Ala92 allele showed a trend towards higher levels of insulin (P = 0·07) and a higher HOMA (P = 0·09).
Conclusion In this population of nondiabetic elderly men, serum thyroid parameters and the TSHR-Asp727Glu polymorphism were associated with relative insulin resistance. Our study suggests that genetic variation in TSHR plays a role in insulin resistance and thereby influences glucose metabolism.
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