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Changes in Plasma Low-Density Lipoprotein (LDL)- and High-Density Lipoprotein Cholesterol in Hypo- and Hyperthyroid Patients Are Related to Changes in Free Thyroxine, Not to Polymorphisms in LDL Receptor or Cholesterol Ester Transfer Protein Genes

Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands

Address correspondence and requests for reprints to: M. J. M. Diekman, Academic Medical Center, Department of Endocrinology and Metabolism F5-174, Meibergdreef 9, 1105 AZ Amsterdam Zuidoost, The Netherlands. E-mail: m.j.diekman{at}amc.uva.nl

Thyroid function disorders lead to changes in lipoprotein metabolism. Both plasma low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) increase in hypothyroidism and decrease in hyperthyroidism. Changes in LDL-C relate to altered clearance of LDL particles caused by changes in expression of LDL receptors on liver cell surfaces. Changes in cholesterol ester transfer activity partly explain changes in HDL-C. It has been suggested that the magnitude of these changes is related to polymorphisms of involved genes. The aim of the present study is to investigate whether the polymorphic AvaII restriction site in exon 13 of the LDL receptor gene and the polymorphic TaqIB site in intron 1 of the cholesterol ester transfer protein are associated with the magnitude of the changes in plasma LDL-C and HDL-C, respectively, in the transition from the hypo- or hyperthyroid to the euthyroid state.

From a consecutive group of 66 untreated hypothyroid and 60 hyperthyroid patients, 47 Caucasians in each group were analyzed. Fasting LDL-C and HDL-C were measured at baseline and 3 months after restoration of the euthyroid state. Genotype was determined by means of PCR techniques. The homozygous presence of a restriction site was designated as +/+, heterozygous as +/-, and absence as -/-. Trend analysis was done with ANOVA.

Among hypo- or hyperthyroid patients, subgroups with different genotypes did not differ in thyroid function pre- or post treatment. The mean decrease in LDL-C (mmol/L ± SD) in hypothyroid patients with different AvaII genotypes did not differ: -1.07 ± 1.44 (-/-, N = 15), -1.25 ± 1.53 (+/-, N = 19), and -1.18 ± 1.01 (+/+, N = 13) mmol/L [not significant (NS)]; neither did the mean increase in hyperthyroid patients: 1.07 ± 0.90 (-/-, N = 18), 0.92 ± 1.00 (+/-, N = 21), and 1.20 ± 0.45 (+/+ N, = 6) (NS). The mean decrease in HDL-C (mmol/L ± SD) in hypothyroid patients with different TaqIB genotypes did not differ: -0.22 ± 0.26 (-/-, N = 13), -0.15 ± 0.23 (+/-, N = 21), and -0.12 ± 0.22 (+/+, N = 9) (NS); neither did the mean increase in hyperthyroid patients: 0.29 ± 0.39 (-/-, N = 7), 0.26 ± 0.23 (+/-, N = 22), and 0.19 ± 0.31 (+/+, N = 18) (NS). Changes in LDL-C and HDL-C correlated with the logarithm of the change in free T₄ (fT₄), expressed as the fT₄ posttreatment/fT₄ pretreatment ratio (r = -0.81, P < 0.001; and r = -0.62, P < 0.001, respectively). In conclusion, in the transition from hypo- or hyperthyroidism to euthyroidism, no association is found between AvaII genotype and changes in plasma LDL-C nor between TaqIB genotype and changes in HDL-C. Changes in LDL-C and HDL-C correlate with changes in fT₄.

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