Associations between the common HNF1A gene variant p.I27L (rs1169288) and risk of type 2 diabetes mellitus are influenced by weight.

ABSTRACT

AIM: The common variants p.I27L (rs1169288), p.A98V (rs1800574) and p.S487N (rs2464196) of the hepatocyte nuclear factor 1-α (HNF1A) gene have been inconsistently associated with impaired glucose tolerance and/or an increased risk of type 2 diabetes mellitus (T2DM). The present study aimed to investigate whether these associations are affected by weight. METHODS: A cross-sectional analysis was conducted among 861 Japanese subjects (males 65.5%; 61.8±12.3years) attending a health-screening programme. Interactive effects between HNF1A variants and weight status on risk of T2DM or dysglycaemic status were determined. RESULTS: The 27L variant carriers were at higher risk of T2DM and dysglycaemic status than non-carriers, but only in normal-weight subjects [odds ratio (OR) 2.04, P=0.03 and OR 2.56, P=0.01, respectively]. An interactive effect of the p.I27L (rs1169288) variant and weight status on the risk of dysglycaemic status was found (P=0.04). Age, but not body mass index (BMI), was a risk factor for dysglycaemic status in the 27L carriers (OR 1.05, P=0.0003), whereas BMI was a risk factor in non-carriers (OR 1.23, P=0.008). No carriers of 98V were identified, and 487N was not associated with either T2DM or dysglycaemic status in our study population. CONCLUSION: These findings suggest that the HNF1A p.I27L (rs1169288) variant may be a significant risk factor of T2DM in normal-weight subjects and that earlier inconsistent results may have been due, in part, to subjects' weight status. Further investigations in larger cohorts are needed to verify these findings.