MIF Promoter Variant rs755622 (-173G/C) in Younger and Older Turkish Adults: An Exploratory Cross-Sectional Genetic...

Age-associated immune-inflammatory remodeling may be influenced by regulatory variation in the macrophage migration inhibitory factor gene (MIF). We conducted an exploratory cross-sectional comparison to assess whether MIF rs755622 (-173G/C) genotype distributions differ between predefined younger and older age groups in a Turkish population and to characterize the observed pattern using genetic-model and in silico analyses. We evaluated 368 individuals: 245 older adults aged 65-102 years and 123 younger controls aged 20-46 years. None of the 26 main association tests remained statistically significant after global multiplicity correction (minimum FDR q = 0.062; minimum Bonferroni-adjusted p = 0.108). Before correction, GC frequency was higher in the older group and increased across the ordered age categories, and sex-adjusted analyses yielded concordant nominal estimates. However, these nominal patterns were sensitive to younger-control genotype reclassification and were not supported by an allele-level or additive association. Younger controls showed Hardy-Weinberg disequilibrium (p < 0.001), without sequencing confirmation, and deterministic and scenario-based Monte Carlo genotype-reclassification analyses indicated sensitivity of the nominal signal to uncertainty in control genotype classification. GTEx data provide C-allele-oriented expression context but do not validate function in this cohort. These preliminary findings warrant independent genotype verification, ancestry-matched replication, and direct functional investigation in future studies.