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The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects.


ABSTRACT: We investigated the association between the loss-of-function mutation MC4R p.Ile269Asn and T2D risk in the Mexican population. We enrolled 6929 adults [3175 T2D cases and 3754 normal glucose tolerant (NGT) controls] and 994 NGT children in the study. Anthropometric data and T2D-related quantitative traits were studied in 994 NGT children and 3754 NGT adults. The MC4R p.Ile269Asn mutation was genotyped using TaqMan. The MC4R p.Ile269Asn mutation was associated with T2D [OR?=?2.00, 95% confidence interval (CI) 1.35-2.97, p?=?0.00057] in Mexican adults. Additional adjustment for body-mass index (BMI) attenuated but did not remove the association (OR?=?1.70, 95% CI 1.13-2.56, p?=?0.011). The MC4R p.Ile269Asn mutation was associated with T2D (OR?=?1.88, 95% CI 1.14-3.08, p?=?0.013) in a subset of 1269 T2D cases and 1269 NGT controls matched for sex, age, and BMI. A mediation analysis estimated that BMI accounts for 22.7% of the association between MC4R p.Ile269Asn mutation and T2D risk (p?=?4.55?×?10-6). An association was observed between the MC4R p.Ile269Asn mutation and BMI in NGT children and adults (children: beta?=?3.731?±?0.958, p?=?0.0001; adults: beta?=?2.269?±?0.536, p?=?2.3?×?10-5). In contrast, the mutation was not associated with T2D-related quantitative traits. We demonstrate that the MC4R p.Ile269Asn mutation predisposes to T2D via obesity-dependent and independent effects in the Mexican population.

PROVIDER: S-EPMC7862248 | BioStudies |

REPOSITORIES: biostudies

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