The Asp727Glu polymorphism in the TSH receptor is associated with insulin resistance in healthy elderly men.
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-Ala(92) allele showed a trend towards higher levels of insulin (P = 0.07) and a higher HOMA (P = 0.09).


CONCLUSIONS
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.
Peeters
Robin P
RP
Department of Internal Medicine, Erasmus University Medical Cetnre, Rotterdam, The Netherlands. r.peeters@erasmusmc.nl
van der Deure
Wendy M
WM
van den Beld
Annewieke W
AW
van Toor
Hans
H
Lamberts
Steven W J
SW
Janssen
Joop A M J L
JA
Uitterlinden
André G
AG
Visser
Theo J
TJ
D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D020738:Leptin / Q000097:blood; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D011989:Receptors, Thyrotropin / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014285:Triiodothyronine, Reverse / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D011989:Receptors, Thyrotropin; D014285:Triiodothyronine, Reverse; D013972:Thyrotropin; D013974:Thyroxine