The cyclin-dependent kinase inhibitor (CDKN/2A) gene locus has been implicated in diabetes type 2 susceptibility through genomewide association studies (GWAS). However, there is paucity of data on this in Nigeria. The aim was to determine association and risks indices of subjects with type 2 diabetes expressing CDKN/2A gene in some tribes in Southern Nigeria. This is a cross-sectional study that involved 120 females and males’ subjects from Ijaw, Ogoni, Ikwerre and Igbo tribes, between the ages of 34 – 84 attending diabetic clinics at two tertiary hospitals. Well-structured questionnaires were randomly administered to the 120 subjects. The result revealed significant associations (p < 0.05) between all examined lifestyle factors and T2D in individuals expressing the CDKN/2A gene. Sedentary individuals showed a strong positive association with T2D (X² = 16.28, p < 0.0001), with elevated relative risk (RR = 1.66) and odds ratio (OR = 3.21). Subjects without a family history of T2D had a higher association (X² = 16.31, p < 0.0001), with increased relative risk (RR = 1.59) and odds ratio (OR = 3.49). Non-smokers exhibited a significant association with T2D (X² = 24.97, p < 0.0001), with reduced relative risk (RR = 0.26) and odds ratio (OR = 0.11). The Ijaw tribe depicted a modest but significant association (X² = 4.09, p = 0.043), with reduced relative risk (RR = 0.75) and odds ratio (OR = 0.56). While Ikwere tribe had a strong negative association (X² = 15.56, p < 0.0001), with reduced relative risk (RR = 0.51) and odds ratio (OR = 0.29). Also, Ogoni tribe had a significant negative association (X² = 10.11, p = 0.0015), with reduced relative risk (RR = 0.61) and odds ratio (OR = 0.39). And Igbo tribe had no significant association. Individuals expressing CDKN/2A gene may have the propensity for risk indices for type 2 diabetes in the study population.