Effect of TSH on Non-Alcoholic Fatty Liver Disease (NAFLD) independent of obesity in children of predominantly Hispanic/Latino ancestry by causal mediation analysis

Nichols, Presley; Pan, Yue; Pavlicová, Martina; Rausch, John C.; Mencin, Ali A.; Thaker, Vidhu

doi:10.1371/journal.pone.0234985

Cited by 5 publications

(4 citation statements)

References 44 publications

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“…Recently, another study [15] reported a strong link between TSH level and NAFLD proved by biopsy, independent of obesity, suggesting that thyroid hormone directly affect the synthesis and metabolism of cholesterol and fatty acids in an autonomous way by regulating the transcription of target genes involved in liver metabolism. However, our study failed to show statistical significance between ALT and TSH levels in lean PCOS, perhaps owing to the normal range of TSH levels in our study.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, several studies [ 12 , 13 ] suggest that higher TSH level is also correlated with metabolic syndrome in PCOS; Emel et al [ 14 ] revealed that obese children demonstrate an increase in TSH levels as the degree of hepatic steatosis increased. Recently, another study [ 15 ] reported a strong link between TSH level and NAFLD proved by biopsy, independent of obesity, suggesting that thyroid hormone directly affect the synthesis and metabolism of cholesterol and fatty acids in an autonomous way by regulating the transcription of target genes involved in liver metabolism. However, our study failed to show statistical significance between ALT and TSH levels in lean PCOS, perhaps owing to the normal range of TSH levels in our study.…”

Section: Discussionmentioning

confidence: 99%

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The Associations Between Alanine Aminotransferase and Other Biochemical Parameters in Lean PCOS

Liu

Zhao

et al. 2022

Reprod. Sci.

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To explore the associations of alanine aminotransferase in lean women of polycystic ovary syndrome (PCOS) with other biochemical parameters and the potential risk factors. This is a retrospective cohort study with lean PCOS (n = 91) and healthy controls (n = 45); we reviewed the electrical records and databases of the PCOS patients in our infertility clinic between January 2019 and September 2021; independent t-test, linear correlation analysis, and multiple linear regression were used to explore the associations. Higher levels of luteinizing hormone, total testosterone, thyroid stimulating hormone, platelet count, lymphocyte count, homocysteine, alanine aminotransferase (ALT), and uric acid were identified in lean PCOS patients, while follicle-stimulating hormone level was lower in in lean PCOS as expected (P < 0.05). Of note, the linear correlation showed that BMI, total testosterone, white blood cell count, lymphocyte count, aspartate aminotransferase, and uric acid were positively associated with alanine aminotransferase (r = 0.232, 0.318, 0.218, 0.388, 0.602, 0.353 respectively, P < 0.05). After multiple linear regression was performed, total testosterone and aspartate aminotransferase were independently and positively correlated with alanine aminotransferase in lean PCOS (B = 0.251, 0.605 respectively, P < 0.05). Higher level of ALT was identified in the lean PCOS. BMI, white blood cell count, lymphocyte count, aspartate aminotransferase, uric acid, and total testosterone were positively correlated with ALT in lean PCOS. Total testosterone and aspartate aminotransferase were independently and positively associated with ALT in lean PCOS after multiple linear regression. There might exist a potential risk of afflicting liver impairment for the lean PCOS women in the earlier period. Early examination and intervention might be necessary to prevent or delay the progression of the liver disease as soon as the diagnosis of PCOS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Associations Between Alanine Aminotransferase and Other Biochemical Parameters in Lean PCOS

Liu

Zhao

et al. 2022

Reprod. Sci.

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“…NAFLD is considered to possess a complex trait resulting from environmental exposures and multiple susceptible genes. Our study is the first research to explore the correlation and causal mediation between TG level and NAFLD in Chinese elderly group even though the mediation effect in our study is not as high as that in Nichols, P. H. et al result - the mediated effect of TSH on NAFLD was 16.0% [ 38 ]. Our mediation analysis showed that TG played a partial mediating role in the relationship between rs1260326 and NAFLD.…”

Section: Discussionmentioning

confidence: 69%

The association between rs1260326 with the risk of NAFLD and the mediation effect of triglyceride on NAFLD in the elderly Chinese Han population

Yuan

Zhan

et al. 2022

Aging

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Background: Accumulated studies have pointed out the striking association between variants in or near APOC3 , GCKR , PNPLA3 , and nonalcoholic fatty liver disease (NAFLD) at various ages from multiple ethnic groups. This association remained unclear in the Chinese Han elderly population, and whether this relationship correlated to any clinical parameters was also unclear. Objectives: This study aims to decipher the complex relevance between gene polymorphisms, clinical parameters, and NAFLD by association study and mediation analysis. Methods: Eight SNPs (rs2854116, rs2854117, rs780093, rs780094, rs1260362, rs738409, rs2294918, and rs2281135) within APOC3 , GCKR, and PNPLA3 were genotyped using the MassARRAY® platform in a large Chinese Han sample comprising of 733 elderly NAFLD patients and 824 age- and ethnic-matched controls. Association and mediation analysis were employed by R. Results: The genotypic frequencies of rs1260326 and rs780094 were significantly different between NAFLD and control (rs1260326: P =0.004, P corr =0.020, OR [95%CI]= 0.69 [0.54-0.89]; rs780094: P =0.005, P corr =0.025, OR [95%CI]= 0.70 [0.55-0.90]). Particularly, an increased triglyceride level was observed in carriers of rs1260326 T allele (1.94±1.19 mmol/L) compared with non-carriers (1.73±1.05 mmol/L).no significant results were observed in rs780094. Notably, triglyceride levels had considerably indirect impacts on association between NAFLD and rs1260326 (β =0.01, 95% CI: 0.01–0.02), indicating that 12.7% of the association of NAFLD with rs1260326 was mediated by triglyceride levels. Conclusions: Our results identified a prominent relationship between GCKR rs1260326 and NAFLD, and highlighted the mediated effect of triglyceride levels on the that association in the Chinese Han elderly.

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“…The rs626283 polymorphism in the MBOAT7 gene has been associated with MASLD in adults, which is believed to be due to increased intrahepatic triglyceride content and inflammation. A study published in 2018 investigated this association within a multiethnic cohort of obese children and adolescents and found that this rs626283 variant in the MBOAT7 gene was associated with MASLD in non-Hispanic White obese children and adolescents but not among Hispanic and Black children and youth, thus showing genetic variation at the pediatric level that does not exist at the adult level [55] .…”

Section: Genetic Studies Investigating Masld In Pediatric Populationsmentioning

confidence: 99%

Racial and ethnic disparities in metabolic dysfunction-associated steatotic liver disease

Gulati,

Moylan,

Wilder

et al. 2024

Metab Target Organ Damage

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Metabolic dysfunction-associated steatotic liver disease (MASLD) has an increasing prevalence, morbidity, and mortality both within the U.S. and globally. Here, we review newer evidence demonstrating racial and ethnic disparities that exist in the incidence of MASLD in the U.S. Many studies demonstrate that Hispanic populations have the highest prevalence of MASLD within the U.S., followed by non-Hispanic White populations and then non-Hispanic Black populations. In addition, we present the latest research investigating specific factors that contribute to these disparities, including genetics, environmental exposures, diet, physical activity, and socioeconomic disparities. Finally, we discuss future directions and interventions needed to increase knowledge of racial and ethnic disparities in MASLD and reduce future disparities. The necessary strategies include increasing diversity and documentation of race and ethnicity in MASLD clinical studies, and increased screening and preventative health education for MASLD in vulnerable populations.

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Effect of TSH on Non-Alcoholic Fatty Liver Disease (NAFLD) independent of obesity in children of predominantly Hispanic/Latino ancestry by causal mediation analysis

Abstract: Background Nonalcoholic Fatty Liver Disease (NAFLD) is a common co-morbidity of obesity. Elevated TSH levels (eTSH), also associated with obesity, may contribute to the dysmetabolic state that predisposes to NAFLD.

Cited by 5 publications

References 44 publications

The Associations Between Alanine Aminotransferase and Other Biochemical Parameters in Lean PCOS

The Associations Between Alanine Aminotransferase and Other Biochemical Parameters in Lean PCOS

The association between rs1260326 with the risk of NAFLD and the mediation effect of triglyceride on NAFLD in the elderly Chinese Han population

Racial and ethnic disparities in metabolic dysfunction-associated steatotic liver disease

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