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Three candidate SNPs show associations with thyroid-stimulating hormone in euthyroid subjects: Tehran thyroid study

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Abstract

Objectives

Previous studies have shown interindividual variation in free thyroxine (FT4) serum levels and thyroid stimulating hormone (TSH) in healthy persons. Genetic factors mainly determine this variation, and genome-wide association studies have increased the number of thyroid function-associated variants. The present study investigates the association of candidate variants with FT4 and TSH in a euthyroid Iranian population.

Method

A total of 2931 unrelated euthyroid subjects (FT4 10.29–21.88 pmol/L; TSH 0.32–10 mIU/L, thyroid peroxidase antibody TPOAb < 33 IU/mL in men and < 35 IU/mL in women), with available genotypes were chosen from the Tehran Thyroid Study (TTS), to examine the impact of selected SNPs on thyroid hormone under the additive genetic model. In order to evaluate regional associations with FT4 and TSH levels, a haplotype analysis was done.

Results

We identified a strong association between the rs4338740-C allele and TSH in the adjusted model (β = -0.095, P-value = 0.0004). Also, findings indicated that rs4954192 ACMSD and rs4445669 CADM1 correlated with normal TSH levels (P-value = 0.011, P-value = 0.014, respectively). Haplotype analysis revealed that two haplotypes were significantly associated with TSH levels in euthyroid individuals. The ACGA and AC haplotypes on chromosomes 8 and 14 were significantly correlated with normal TSH levels, respectively (P-value = 0.014, P-value = 0.016).

Conclusions

This is the first genetic association study with TSH and FT4 reference values in an Iranian population. Our findings indicate that a few gene variants associated with the reference values of TSH in other populations are also associated with the reference values of TSH in Iranians.

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Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request after permission from the Endocrine and Metabolism Research Center of the Shahid Beheshti University of Medical Science.

Abbreviations

(GWAS):

Genome-wide association studies

(SNP):

Single nucleotide polymorphism

(TCGS):

Tehran Cardiometabolic Genetic Study

(TLGS):

Tehran Lipid and Glucose Study

(TTS):

Tehran thyroid study

(HWE):

Hardy–Weinberg equilibrium

(LDL):

Low-density lipoprotein

(HDL):

High-density lipoprotein

(SBP):

Systolic blood pressure

(DBP):

Diastolic blood pressure

(TG):

Triglyceride

(Chol):

Cholesterol

(BMI):

Body mass index

(TSH):

Thyroid-stimulating Hormone

(FT4):

Free thyroxine

(FGF7):

Fibroblast growth factor 7

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Acknowledgements

The authors would like to thank Dr. MirAlireza Takyar for his guidance and suggestions for marker selection.

Funding

This study was supported in part by Grant No 28741–7 from Shahid Beheshti University of Medical Sciences.

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Authors and Affiliations

  1. Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Azita Zadeh-Vakili, Hengameh Abdi & Fereidoun Azizi

  2. Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Parvaneh St, Yemen St, Chamran Exp, PO Box 1985717413, Tehran, IR, Iran

    Leila Najd-Hassan-Bonab, Mahdi Akbarzadeh, Asiyeh Sadat Zahedi & Maryam S. Daneshpour

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  1. Azita Zadeh-Vakili
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Correspondence to Maryam S. Daneshpour.

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The authors declare that they have no conflict of interest.

Study concept and design

AZ, MSD, HA. Acquisition of data: LNHB, ASZ. Analysis and interpretation of data: LNHB, MA, AZ. Drafting of the manuscript: AZ, LNHB, FA. Critical revision of the manuscript for important intellectual content AZ, MSD, HA, FA, MA. Statistical analysis: MA, LNHB. Administrative, technical, and material support: FA, MSD, HA. Study supervision: FA, MSD, AZ.

All authors discussed the results and contributed to the final manuscript.

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Zadeh-Vakili, A., Najd-Hassan-Bonab, L., Akbarzadeh, M. et al. Three candidate SNPs show associations with thyroid-stimulating hormone in euthyroid subjects: Tehran thyroid study. J Diabetes Metab Disord (2024). https://doi.org/10.1007/s40200-023-01383-2

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