When participants were stratified by baseline smoking status, HNF1A G319S carriers who were active smokers had increased risk of developing diabetes (OR 6.91 [95% CI 3.38-14.12]), while the association was attenuated to non-significance among non-smokers (1.11 [0.40-3.08]).
The influence of exposure to diabetes in utero and the HNF-1α G319S polymorphism on the metabolic phenotype of youth with T2DM at diagnosis is unknown.
We aimed to investigate whether CRP was mediating the association between HNF1A G319S and type 2 diabetes in an Aboriginal Canadian population with a high prevalence of diabetes.
The demonstration of a functional consequence for HNF1A G319S provides a mechanistic basis for its strong association with Oji-Cree type 2 diabetes and its unparalleled specificity for diabetes prediction in these people, in whom diabetes presents a significant public health dilemma.
Despite the failure of linkage analysis to identify HNF1A as a determinant of type 2 diabetes, we feel justified in interpreting that G319S has a very important pathogenic role in Oji-Cree diabetes, based upon the highly suggestive association studies.