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- Title
127L Variant of HNF-1α Gene May Change Mutual Relationship of Metabolic Syndrome Features in Autossomal Dominant Type 2 Diabetes Mellitus.
- Authors
Giuffrida, Fernando; Furuzawa, Gilberto; Kasamatsu, Teresa; Reis, Andre F.; Dib, Sergio A.
- Abstract
Type 2 Diabetes Mellitus (T2DM) is a geneticaly and clinically heterogeneous disease. Few genes have been associated to T2DM to date, in selected populations. Variants in hepatocyte nuclear factor (HNF)-1α are associated with insulin secretion and Metabolic Syndrome (MS) in normal individuals, but their influence in T2DM and associated MS is not well understood. Eighteen patients with autossomal dominant diabetes (3 generations, uniparental lineage) and late-onset (age at diagnosis >40 y.o in all family members) (ADD group), as well as 32 classical T2DM (CT2D group) controls (late-onset, inheritance pattern other than above described) have been evaluated in a cross-sectional study regarding clinical and laboratory features of MS according to the NCEP criteria. The entire HNF-1α gene has been directly sequenced. Groups had similar age (68[59-74.3] vs. 64[58.3-68] yo), time from diagnosis (1216-18] vs. 11[8-14] y), BMI (28.8±4.4 vs. 29±4.9 kg/m²), waist circumference (W)(99.5±13.4 vs. 100±12.1cm), A1c (7.3±0.9 vs. 7.2±1%), triglycerides (TG) (108.5191-161] vs. 133.5192.5-184]mg/dL), HDL (44.5±11.5 vs. 47.6±14.1mg/dL), prevalence of hypertension (72.2 vs 93.8%) and MS (77.8% vs 87.5%). The HNF-1α SNP I27L was found in 66.7% of ADD and 35.5% of CT2D (p<0.05). BMI correlated negatively to HDL (r=-0.55; p<0.005) and positively with TG (r=0.59; p<0.002) in CT2D, but positively with HDL (r=0.67; p<0.03) in ADD group. Logistic regression (LR) showed marginal protective e fleet of the SNP for hypertriglyceridemia (p=0.055) in group ADD. Redividing the total group in I27L and I27I genotypes (regardless of inheritance pattern), 127L individuals show higher BMI (29.4[27.1-31.8] vs. 26.8[24.3-30.4]kg/m²) and W (104.6+13.2 vs. 95.8+10.7cm), but similar waist-to-hip ratio (WHR). Similarly to CT2D, TG correlated to BMI only in I271 (r=0.53; p<0.02). TG were correlated to HOMAIR>2 in 127L (p<0.05; LR), but not to some insulin resistance (IR) markers. These preliminary data suggest obesity to carry a different metabolic significance in ADD and CT2D groups. The analogy between ADDxCT2D and I27IxI27L comparisons point to a role of the SNP on the observed differences. This group of ADD clinically fits in the heterogeneity of T2DM, but with increased prevalence of I27L. Presence of this variant could be useful in separating a group within T2D in which obesity, visceral adiposity and IR do not bear an as close as expected relationship.
- Subjects
METABOLIC syndrome; TYPE 2 diabetes; HEPATOCYTE growth factor; INSULIN; TRIGLYCERIDES; HYPERTENSION; HYPERTRIGLYCERIDEMIA; OBESITY
- Publication
Diabetes, 2007, Vol 56, pA644
- ISSN
0012-1797
- Publication type
Article