Association between TNF-α -308G>A (rs1800629) polymorphism and non-invasive liver fibrosis indices in non-MASLD adults

Nguyen Huu Ngoc Tuan, Nguyen Minh Ha

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Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rising globally, and subclinical fibrosis can occur even in lean or apparently healthy adults, requiring reliable non-invasive screening tools at primary care. APRI and FIB-4 are common indices, yet their baseline performance in pre-MASLD groups and potential bias from the pro-inflammatory TNF-α -308G>A (rs1800629) polymorphism remain uncertain in Vietnamese adults. This secondary cross-sectional study analyzed 240 adults from a prospective occupational cohort without MASLD or chronic liver disease. Genotyping of rs1800629 used PCR-RFLP and Sanger sequencing; APRI and FIB-4 scores derived from fasting AST, ALT, platelet count, and age. Using multivariable OLS linear regression and logistic regression models (dominant model: GA/AA vs GG), adjusted for age, sex, BMI, and HBsAg, the polymorphism showed no independent association with APRI (β = -0.0141, p = 0.444) or FIB-4 (β = -0.0025, p = 0.967). Male sex was significantly associated with higher APRI (p < 0.001) due to a physiological increase in AST and a decrease in platelets, whereas FIB-4 showed greater stability (p = 0.831). Therefore, in non-MASLD Vietnamese adults, TNF-α rs1800629 showed no significant association with fibrosis indices, suggesting FIB-4's greater stability for routine screening in primary healthcare.

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References

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