PNPLA3 polymorphism influences the association between high-normal TSH level and NASH in euthyroid adults with biopsy-proven NAFLD - 20/11/20

Doi : 10.1016/j.diabet.2020.02.001

D.-S. Hu ^a, S.-H. Zhu ^a, W.-Y. Liu ^b, X.-Y. Pan ^b, P.-W. Zhu ^c, Y.-Y. Li ^d, K.I. Zheng ^e, H.-L. Ma ^e, J. You ^f, G. Targher ^g, C.D. Byrne ^h, Y.-P. Chen ^e,^i,^j, M.-H. Zheng ^e,^i,^j,⁎
^a Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
^b Department of Endocrinology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
^c Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
^d Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
^e NAFLD Research Centre, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
^f Department of Thyroid and Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
^g Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
^h Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
ⁱ Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
^j Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China

^⁎Corresponding author at: NAFLD Research Centre, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou 325000, China.NAFLD Research Centre, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical UniversityNo. 2 Fuxue LaneWenzhou 325000China

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Abstract

Aim

We aimed to evaluate the association between serum thyroid stimulating hormone (TSH) levels, within the reference range, and the histological severity of nonalcoholic fatty liver disease (NAFLD), and whether this association was modulated by the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism.

Materials and methods

We enrolled 327 euthyroid individuals with biopsy-proven NAFLD, who were subdivided into two groups, i.e., a ‘strict-normal’ TSH group (TSH level 0.4 to 2.5mIU/L; n=283) and a ‘high-normal’ TSH group (TSH level 2.5 to 5.3mIU/L with normal thyroid hormones; n=44). Logistic regression analyses were performed to assess the association between TSH status and presence of nonalcoholic steatohepatitis (NASH) after stratifying subjects by PNPLA3 genotypes.

Results

Compared to strict-normal TSH group, patients with high-normal TSH levels were younger and had a greater prevalence of NASH and higher histologic NAFLD activity score. After stratifying by PNPLA3 genotypes, the significant association between high-normal TSH levels and presence of NASH was restricted only to carriers of the PNPLA3 G risk allele and remained significant even after adjustment for potential confounding factors (adjusted-odds ratio: 3.279; 95% CI: 1.298–8.284; P=0.012).

Conclusion

In euthyroid individuals with biopsy-proven NAFLD, we found a significant association between high-normal TSH levels and NASH. After stratifying by PNPLA3 rs738409 genotypes, this association was observed only among carriers of the PNPLA3 G risk allele.

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Keywords : Euthyroidism, NASH, PNPLA3, TSH

Abbreviations : NAFLD, PNPLA3, NASH, CI, HCC, TSH, FT4, FT3, NAS, ALT, AST, BMI, WBC, HDL-C, HOMA-IR, LDL-C, OR, SD, GGT, HSL, ATLG, SREBP1c, SRE

Plan

Introduction

Materials and methods

Study population

Liver histology

Analysis of the PNPLA3 rs738409 polymorphism

Clinical, laboratory data and thyroid function testing

Statistical analysis

Results

Baseline characteristics of patients stratified by NASH status

Baseline characteristics of patients stratified by TSH status

Baseline characteristics of patients stratified by TSH status and PNPLA3 rs738409 genotypes

High-normal TSH levels and increased risk of having NASH in carriers of the PNPLA3 G risk allele

Discussion

Conclusion

Funding sources

Authors’ contributions

Disclosure of interest

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Vol 46 - N° 6

P. 496-503 - novembre 2020 Retour au numéro

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PNPLA3 polymorphism influences the association between high-normal TSH level and NASH in euthyroid adults with biopsy-proven NAFLD - 20/11/20

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Results

Conclusion

Plan

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