Stat4 rs7574865 polymorphism promotes the occurrence and progression of hepatocellular carcinoma via the Stat4/CYP2E1/FGL2 pathway

Wang, Caie; Gao, Na; Yang, Lukui; Guo, Yuanyuan; Fang, Yan; Wang, Tong; Xu, Chen; Li, Gui fang; Zhou, Jun; Zhang, Yunfei; Wen, Qiang; Qiao, Huan

doi:10.1038/s41419-022-04584-4

Cited by 6 publications

(4 citation statements)

References 49 publications

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“…El Sharkawy et al have recently confirmed that a risk STAT4 SNP in a Caucasian population is associated with a greater rate of fibrosis and inflammation in HBV patients [22]. The same effects have been described in Asian populations [23,34,36,37]. It is also possible that inflammatory mechanisms leading to different immune active mechanisms related to STAT activation or inactivation are present in certain populations compared to others, affecting HCC risk [20,46,47].…”

Section: Discussionmentioning

confidence: 82%

“…STAT4 functions as a mediator of immunity and tumor growth as an important member of the JAK-STAT pathway. It has been associated with autoimmune diseases [ 31 , 32 ] and malignancies such as lung, colon, and breast cancer [ 22 , 23 , 33 , 34 , 35 , 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…While other studies, such as the replication study by Chen et al, failed to repeat the same findings [ 20 ]. However, these studies have been performed in Asian and Caucasian populations with no representation of other ethnic groups [ 14 , 20 , 21 , 22 , 23 ]. Supplementary Table S1 describes all previous studies on STAT4 and HCC and their methodologies.…”

Section: Introductionmentioning

confidence: 99%

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Assessment of STAT4 Variants and Risk of Hepatocellular Carcinoma in Latin Americans and Europeans

Ayoub,

Anugwom,

Prieto

et al. 2023

Cancers

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Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The STAT4 rs7574865 genetic variant has been associated with an increased risk of developing HCC in Asian populations. However, this association has not been studied in Latin America and is poorly assessed in European populations. This case-control study investigated the association between STAT4 rs7574865 and HCC risk in these populations. We evaluated DNA samples from seven medical institutions across six Latin American countries and one Dutch institution in 1060 individuals (344 HCC and 716 controls). STAT4 rs7574865 SNP was genotyped using TaqMan-genotyping assay and analyzed using logistic regression. We found no significant association between the homozygous risk allele (G) of STAT4 and HCC development in either population, with odds ratios (OR) for GG versus TT of 0.85 (CI: 0.48–1.52, p = 0.58) and 0.81 (CI: 0.34–1.93, p = 0.67) for Latin Americans and Europeans respectively. No correlation was found between the risk allele and HCC based on underlying liver disease. However, we found that Latin Americans of European ancestry were more likely to carry the risk allele. Our results suggest that the STAT4 SNP rs7574865 does not influence the risk of developing HCC in Latin American or European populations, highlighting the importance of evaluating genetic risk factors in various ethnic groups and understanding the possible influence of ancestry on the genetic basis of disease.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Assessment of STAT4 Variants and Risk of Hepatocellular Carcinoma in Latin Americans and Europeans

Ayoub,

Anugwom,

Prieto

et al. 2023

Cancers

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“…For instance, the rs7574865 polymorphism of the STAT4 gene is a G > T change in the third intron, which has been associated with its TT polymorphic genotype with the increased presence of autoimmunity. In patients with SLE, the polymorphic variant has been identified as being associated with increased susceptibility to presenting with the disease, as well as an increased risk of presenting positive autoantibodies [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus

Esparza-Guerrero

Villegas

Valdivia

et al. 2023

Genes

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STAT4 plays an important role in disease activity in SLE patients. STAT4 particles have the capacity to activate the transcription of genes associated with the production of TH1 and Th17 lymphocytes, with a greater predominance on the production of IFN-γ and IL-17A. The presence of variants in STAT4 genes has a major impact on the generation of autoimmunity. However, there are few studies evaluating the impact of these variants on the production of proinflammatory cytokines such as IFN-γ and IL-17A. Methods—A case–control study was carried out with 206 Mexican mestizo patients residing in Western Mexico with a diagnosis of SLE and a group of 80 patients without autoimmune diseases was captured to determine the cut-off point for high IFN-γ levels. In this study, SLE patients with high IFN-γ levels were considered as cases (cut-off > 15.6 pg/mL), and SLE patients with normal IFN-γ levels were considered as controls (cut-off ≤ 15.6 pg/mL). Disease activity was identified from the systemic lupus erythematosus disease activity index (SLEDAI). For the determination of levels of cytokines IFN-γ, IL-12, and IL17A, commercial ELISA kits were used. Genotyping of STAT4 rs7574865 (G > T) was performed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. Results—The patients with SLE had a median age of 45 years with a range of disease duration from 4 years to 18 years; 45.6% were identified as having disease activity. In this sample, we identified a high IFN-γ prevalence of 35.4%. The levels of IFN-γ were higher in the patients with genotype TT than GG. We found that TT genotype conferred a higher risk of high IFN-γ when compared to the GG and GT genotypes. Conclusions—In this study, we identified that the polymorphic genotype TT of the STAT4 gene rs7574865 polymorphism is associated with increased levels of IFN-γ. However, its strength of association was weak, so complementary studies are needed to evaluate its impact on SLE patients.

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STAT4 regulates cardiomyocyte apoptosis in rat models of diabetic cardiomyopathy

He¹,

Li²,

Guo³

2022

Acta Histochemica

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Stat4 rs7574865 polymorphism promotes the occurrence and progression of hepatocellular carcinoma via the Stat4/CYP2E1/FGL2 pathway

Cited by 6 publications

References 49 publications

Assessment of STAT4 Variants and Risk of Hepatocellular Carcinoma in Latin Americans and Europeans

Assessment of STAT4 Variants and Risk of Hepatocellular Carcinoma in Latin Americans and Europeans

Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus

STAT4 regulates cardiomyocyte apoptosis in rat models of diabetic cardiomyopathy

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