Exploring the Association of FTO rs9939609 with Type 2 Diabetes, Fasting Glucose and HbA1c in a Southeastern Mexican Region of Predominant Mayan Genetic Background

Type 2 diabetes (T2D) is a multifactorial disease characterized by chronic hyperglycemia. The <i>FTO</i> variant rs9939609 has been widely associated with obesity, but emerging evidence suggests a broader role for T2D risk across diverse populations. However, Mayan ancestry individuals remain underrepresented in genetic studies. Thus, we evaluated the association of rs9939609 with T2D, fasting glucose, and HbA1c in a southeastern Mexican region with prevalent Mayan ancestry. Birthplace was used as a proxy for ancestry, although no formal ancestry assessment was conducted. The A allele was associated with increased risk for T2D in both additive (OR = 1.88 [1.08-3.40], <i>p</i> = 0.031) and dominant (OR = 2.09 [1.08-4.15], <i>p</i> = 0.032) models, even after adjusting for age, sex, BMI, waist circumference, and waist/hip ratio. The A allele was also associated with increased fasting glucose and HbA1c levels in the dominant model. Mediation analysis suggested that T2D may mediate the effect of rs9939609-A on glucose traits. rs9939609-A may be a risk factor for T2D and elevated glucose levels in this population. However, the results should be interpreted with caution due to the limited sample size, which may result in under- or overestimation of effect sizes.