Serum gp91phox/NOX2 Level Among Patients with Subclinical Hypothyroidism, and Its Relation to Atherogenic Indices

Ekhlas Ali  Sulaiman; Sherwan Ferman  Salih; Dhia Mustafa  Sulaiman

doi:10.56056/amj.2025.350

Authors

Ekhlas Ali Sulaiman MBChB, Kurdistan Higher Council candidate for medical specialties KHCMS/ Chemical Pathology, Azadi Teaching Hospital, Duhok
Sherwan Ferman Salih MBChB- FIBMS (chemical pathology), Assistant Professor in Clinical Biochemistry, University of Duhok-college of Medicine
Dhia Mustafa Sulaiman MB Ch B, Msc,Ph.D, Assistant Professor in Clinical Biochemistry and Metabolic Medicine, Duhok Polytechnic University

DOI:

https://doi.org/10.56056/amj.2025.350

Keywords:

Atherogenic indexes, Gp91phox/NOX2, SCH, Subclinical hypothyroidism

Abstract

Background and objectives: Subclinical hypothyroidism is emphasized by a normal serum-free thyroxin4 concentration as well as an elevated thyroid stimulating hormone concentration, Gp91^phox, the catalytic key of nicotinamide-adenine-dinucleotide-phosphate-oxidase and predictor of its activation, has lately been examined as an indicator of systemic oxidative. The current study aimed to assess the level of serum gp91phox among patients with subclinical hypothyroidism.

Methods: The current case-control study included 160 participants: 80 newly diagnosed subclinical hypothyroidism patients were obtained from the Diabetic and Endocrinology Unit at Azadi Teaching Hospital, and 80 healthy individuals, lasted eight months from November 2022 to July 2023. Lipid profile and thyroid function tests have been done for. The serum soluble gp91phox level was compared between both groups.

Results: The mean serum gp91phox was higher among subclinical hypothyroidism cases (9.06 ± 4.80 ng/mL) than among healthy individuals (7.40 ±3.42 ng/mL). There was a statistically significant elevation of the mean of atherogenic-index of plasma in cases (0.39, p. value = 0.049) compared to the controls (0.30, p. value = 0.049), and the mean of Castelli Risk Index II in cases (2.18, p. value = 0.008) was significantly greater than that of the controls (1.86, p. value = 0.008) in subclinical hypothyroidism.

Conclusion: There was a significantly higher mean serum level of gp91^phox/NOX2 in patients with subclinical hypothyroidism.

Downloads

Download data is not yet available.

References

Chaker L, Cappola AR, Mooijaart SP, Peeters RP. Clinical aspects of thyroid function during ageing. Lancet Diabetes Endocrinol. 2018 Sep;6(9):733-742. doi: 10.1016/S2213-8587(18)30028-7. Epub 2018 Jul 17.

Wu K, Zhou Y, Ke S, Huang J, Gao X, Li B, et al. Lifestyle is associated with thyroid function in subclinical hypothyroidism: a cross-sectional study. BMC Endocr Disord. 2021 May 28;21(1):112.

Gosi SY, Garla VV. Subclinical Hypothyroidism. Treasure Island (FL): StatPearls Publishing; 2024 Jan.

Razvi S, Weaver JU, Pearce SH. Subclinical thyroid disorders: significance and clinical impact. J Clin Pathol. 2010 May;63(5):379-86. doi: 10.1136/jcp.2008.057414/

Bhardwaj S, Bhattacharjee J, Bhatnagar MK, Tyagi S. Atherogenic index of plasma, Castelli risk index and atherogenic coefficient - new parameters in assessing cardiovascular risk. Int J Pharm Bio Sci. 2013 Jul-Sep;3(3):359-364.

Abid HA, Abid ZS, Abid SA. Atherogenic indices in clinical practice and biomedical research: A short review. BJBABS. 2021;2(2):52. DOI: https://doi.org/10.47419/bjbabs.v2i02.52/

Sujatha R, Kavitha S. Atherogenic indices in stroke patients: A retrospective study. Iran J Neurol. 2017 Apr 4;16(2):78–82. PMID: 28761629; PMCID: PMC5526781.

Abdullah BI, Salih SF. Lipoprotein (a) level among patients with type 2 diabetes mellitus and prediabetes in comparison with healthy controls. SJUOZ. 2023;11(1):996. DOI: https://doi.org/10.25271/sjuoz.2023.11.1.996/

Ma X, Wang F, Zhen X, Zhao L, Fang L, Dong Z, et al. gp91phox, a novel biomarker evaluating oxidative stress, is elevated in subclinical hypothyroidism. Int J Endocrinol. 2020 May 6; 2020:3161730. doi: 10.1155/2020/3161730. Epub 2020.

Öztürk Ü, Vural P, Özderya A, Karada B, Doru-Abbasolu S, Uysal M. Oxidative stress parameters in serum and low density lipoproteins of Hashimoto's thyroiditis patients with subclinical and overt hypothyroidism. Int Immunopharmacol. 2012 Dec;14(4):349-352. doi: 10.1016/j.intimp.2012.08.010. Epub 2012 Aug 28.

Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000 Nov 9;408(6809):239-247. doi: 10.1038/35041687/

Sedeek M, Hébert RL, Kennedy CR, Burns KD, Touyz RM. Molecular mechanisms of hypertension: role of Nox family NADPH oxidases. Curr Opin Nephrol Hypertens. 2009 Mar;18(2):122-7.

Cangemi R, Celestini A, Calvieri C, Carnevale R, Pastori D, Nocella C, et al. Different behaviour of NOX2 activation in patients with paroxysmal/persistent or permanent atrial fibrillation. Heart. 2012 Jul;98(14):1063-6.

Salih S.F. The prevalence of thyroid dysfunction among women with type 2 diabetes mellitus in Duhok. Duhok Medical J. 2015; 9(2): 52-59.

Weir CB, Jan A. BMI Classification Percentile and Cut Off Points. Treasure Island (FL): StatPearls; 2023 Jun 26. PMID: 31082114 Bookshelf ID: NBK541070.

Gokbulut P, Koc G, Kuskonmaz SM, Onder CE, Omma T, Frat S, et al. High thyroperoxidase antibody titers may predict response to antithyroid drug treatment in Graves disease: a preliminary study. Acta Endocrinol (Buchar). 2023 Apr-Jun;19(2):195-200.

Rastgooye Haghi A, Solhjoo M, Tavakoli MH. Correlation Between Subclinical Hypothyroidism and Dyslipidemia. Iran J Pathol. 2017 Spring;12(2):106–111. PMCID: PMC5831065. PMID: 29515631.

Olamoyegun MA, Oluyombo R, Asaolu SO. Evaluation of dyslipidemia, lipid ratios, and atherogenic index as cardiovascular risk factors among semi-urban dwellers in Nigeria. Ann Afr Med. 2016 Oct-Dec;15(4):194-199. doi: 10.4103/1596-3519.194280. PMID: 27853034; PMCID: PMC5402827/

Cebeci E, Alibaz-Oner F, Usta M, Yurdakul S, Erguney M. Evaluation of oxidative stress, the activities of paraoxonase and arylesterase in patients with subclinical hypothyroidism. J Investig Med. 2012 Jan;60(1):23-28. doi: 10.2310/JIM.0b013e31823581dd. PMID: 21997314.

Wang HC, Dragoo J, Zhou Q, Klein JR. An intrinsic thyrotropin-mediated pathway of TNF-alpha production by bone marrow cells. Blood. 2003 Jan 1;101(1):119-123. doi: 10.1182/blood-2002-02-0544. Epub 2002 Jun 28. PMID: 12393601.

Closs C, Vargas-Uricoechea H, Schwarzstein D, Lobo M, Lagranja E, Godinez-Leiva E, et al. Relationship of Subclinical Hypothyroidism on Epicardial Adipose Tissue: A Systematic Review and Meta-Analysis. Curr Probl Cardiol. 2023 Jul;48(7):101674. doi: 10.1016/j.cpcardiol.2023.101674. Epub 2023 Feb 24. PMID: 36841317.

Camarena V, Sant D, Mohseni M, Salerno T, Zaleski ML, Wang G, et al. Novel atherogenic pathways from the differential transcriptome analysis of diabetic epicardial adipose tissue. Comparative Study. Nutr Metab Cardiovasc Dis. 2017 Aug;27(8):739-750. doi: 10.1016/j.numecd.2017.05.010. Epub 2017 Jun 10. PMID: 28739185; PMCID: PMC7540222.

Solanki A, Bansal S, Jindal S, Saxena V, Shukla US. Relationship of serum thyroid stimulating hormone with body mass index in healthy adults. Indian J Endocrinol Metab. 2013 Oct;17(Suppl 1): S167-S169. doi: 10.4103/2230-8210.119560. PMID: 24251146; PMCID: PMC3830292.

Feldt-Rasmussen U. Thyroid and leptin. Review. Thyroid. 2007 May;17(5):413-419. doi: 10.1089/thy.2007.0032. PMID: 17542671.

Zhang J, Huang C, Meng Z, Fan Y, Yang Q, Zhang W, et al. Gender-Specific Differences on the Association of Hypertension with Subclinical Thyroid Dysfunction. Int J Endocrinol. 2019 Dec 30; 2019:6053068. doi: 10.1155/2019/6053068. PMID: 32082373; PMCID: PMC7012202.

Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P. Autoimmune thyroid disorders. Review. Autoimmun Rev. 2015 Feb;14(2):174-180. doi: 10.1016/j.autrev.2014.10.016. Epub 2014 Oct 25. PMID: 25461470.

Karthick N, Dillara K, Poornima KN, Subhasini AS. Dyslipidaemic Changes in Women with Subclinical Hypothyroidism. J Clin Diagn Res. 2013 Oct;7(10):2122-2125. doi: 10.7860/JCDR/2013/5777.3448/

Blum MR, Gencer B, Adam L, Feller M, Collet TH, da Costa BR, et al. Impact of Thyroid Hormone Therapy on Atherosclerosis in the Elderly with Subclinical Hypothyroidism: A Randomized Trial. J Clin Endocrinol Metab. 2018 Aug 1;103(8):2988-2997. doi: 10.1210/jc.2018-00279. PMID: 29846630.

Sasikala T, Goswami K. Castelli risk index-1 and atherogenic coefficient are better predictors of cardiometabolic risk in patients with hypothyroidism. Int J Clin Biochem Res. 2020;7(2):254-259. doi: 10.18231/j.ijcbr.2020.055/

Qasim B, Arif S, Mohammed A, Abduljabbar R. Dyslipidemia in Subclinical Hypothyroidism: A Case-Control Study. J Endocrinol Diab. 2018;5(1):1-6. DOI: 10.15226/2374-6890/5/1/00192/

Axelband F, Dias J, Ferrão FM, Einicker-Lamas M. Nongenomic signaling pathways triggered by thyroid hormones and their metabolite 3-iodothyronamine on the cardiovascular system. Review. J Cell Physiol. 2011 Jan;226(1):21-28. doi: 10.1002/jcp.22325. PMID: 20658515.

Rizos CV, Elisaf MS, Liberopoulos EN. Effects of Thyroid Dysfunction on Lipid Profile. Open Cardiovasc Med J. 2011; 5:76–84. doi: 10.2174/1874192401105010076. PMID: 21660244; PMCID: PMC3109527.