Exploring the Relationship of rs2802292 with Diabetes and NAFLD in a Southern Italian Cohort-Nutrihep Study.
Level 4 - case-series / case-control
Cross-sectional genetic association study within a single regional cohort
PubMed 39273459 · doi:10.3390/ijms25179512
What was done
Researchers genotyped the FOXO3 rs2802292 variant in 650 middle-aged individuals from a small city in Southern Italy as part of the Nutrihep Study. Lifestyle, dietary habits, and clinical characteristics were recorded from interviews and blood samples. Associations between rs2802292, type 2 diabetes, and NAFLD were evaluated using multivariable logistic regression and mediation analysis adjusted for covariates.
What was found
The TT genotype of rs2802292 was associated with higher odds of diabetes (OR = 2.14, 95% CI 1.01 to 4.53, p = 0.05), whereas possessing the G-allele was associated with lower odds of diabetes (OR = 0.45, 95% CI 0.25 to 0.81, p = 0.008). No direct association was found between rs2802292 and NAFLD, but mediation analysis identified an indirect effect mediated through diabetes, with a direct association between the TT genotype and diabetes (β = 0.10, 95% CI -0.003 to 0.12, p = 0.04).
Why it matters
These findings suggest that the FOXO3 longevity-associated variant may provide metabolic protection against type 2 diabetes, which secondarily reduces the burden of NAFLD.
Limits
The study is observational and cross-sectional, precluding causal inference. The cohort is relatively small (n = 650) and restricted to a single town in Southern Italy, limiting generalizability. Diagnostic definitions for NAFLD and specific covariate adjustments were not described in the abstract.
Cited by
- contradicts The FOXO3A TT genotype has been consistently associated with human longevity and plays a protective role against oxidative stress, apoptosis, DNA repair, immune cell regulation, and stem cell maintenance.