Genotype and Visceral Adiposity Interactions on Hepatic Steatosis in Mexican Adults
Wendolyn E Dávila-Olmedo, Ana T Arias-Marroquín, Fabiola M Del Razo-Olvera, Paloma Almeda-Valdes, Ivette Cruz Bautista, Donaji V Gómez-Velasco, César E Lam-Chung, Alejandro Campos Muñóz, Berenice Rivera-Paredez, Paola Vázquez-Cárdenas, Gabriela A Galán-Ramírez, Alexandro J Martagón-Rosado, Liliana Juárez-Martínez, Rodrigo Otero-Otero, Francisco Álvarez-Molina, Alicia Huerta-Chagoya, Ana Ochoa-Guzmán, Teresa Tusie-Luna, Roopa Mehta, Ricardo U Macías-Rodriguez, Carlos A Aguilar-Salinas, Adrián Soto-MotaAbstract
Background
The SLC16A11 haplotype has been associated with type 2 diabetes (T2D) in populations with high Native American ancestry; however, its role in hepatic outcomes remains uncertain. We evaluated the association of rs13342232 with non-invasive liver markers and whether visceral adiposity (VAT) modifies this relationship in Mexican adults with and without T2D.
Methods
We included 607 adults (non-T2D, n = 256, T2D, n = 351) with genotype, VAT, and Fatty Liver Index (FLI) data. Hepatic steatosis was additionally assessed using FibroScan-derived controlled attenuation parameter and steatosis grade in 301 participants. Multivariable regression models with VAT × rs13342232 interaction terms were fitted, adjusting for ancestry principal components.
Results
A significant VAT × G/G interaction on FLI was observed in the full sample (β = 3.19, 95% CI 0.23–6.15; p = 0.035). The interaction was markedly stronger in adults without T2D (β = 7.51, 95% CI 1.23–13.78; p = 0.018) than in those with T2D (β = 2.00, 95% CI −0.43 to 4.42; p = 0.105), suggesting that the gene-environment effect is most clearly expressed before diabetes onset. Null findings for both the A/G interaction and the dominant model in the non-T2D stratum support a recessive inheritance pattern. FibroScan validation confirmed a VAT × G/G interaction on steatosis grade in non-T2D participants (β = 0.50, 95% CI 0.01–0.99; p = 0.044). In the T2D stratum, a significant negative A/G × VAT interaction was observed (β = −1.63, p = 0.046), indicating heterozygote attenuation of the VAT–steatosis relationship.
Conclusions
The SLC16A11 rs13342232 G/G genotype amplifies the hepatic steatosis response to visceral adiposity in Mexican adults. This effect is strongest prior to diabetes onset, supporting a gene–environment interaction in hepatic fat accumulation.