HNF1A gene variants and cardiovascular risk factors in individuals with late-onset autosomal dominant diabetes: a cross-sectional study Export

@article{citeulike:4746391, abstract = {Background:\&\#10;Type 2 diabetes mellitus (T2DM) is a genetically heterogeneous disease, hepatocyte nuclear factor-1 homeobox A (HNF1A) single-nucleotide polymorphisms (SNPs) playing a minor role in its pathogenesis. HNF1A is a frequent cause of monogenic diabetes, albeit with early-onset. Some uncommon subgroups like late-onset autosomal dominant diabetes mellitus (LOADDM) may present peculiar inheritance patterns with a stronger familial component. This study aims to investigate the relationship of HNF1A SNPs with cardiovascular risk factors in this group, as well as to characterize them in contrast with classical T2DM (CT2DM).\&\#10;Methods:\&\#10;eighteen LOADDM (age at onset > 40 y.o.; diabetes in 3 contiguous generations, uniparental lineage) along with 48 CT2DM patients and 42 normoglycemic controls (N group) have been evaluated for cardiovascular risk factors and SNPs of HNF1A.\&\#10;Results:\&\#10;LOADDM showed significantly higher frequencies of SNPs A98V (22.2\% vs 2.1\%, p=0.02) and S487N (72.2\% vs 43.8\%, p=0.049) of HNF1A compared to CT2DM. I27L did not show significant difference (66.7\% vs 45.8\%), but associated with lower risk of hypertriglyceridemia (OR 0.16, 95\% CI 0.04-0.65, p=0.01). "Protective effect" was independent from other well-known predictive risk factors for hypertriglyceridemia, such as waist circumference (OR 1.09 per 1 cm increase, p=0.01) and HDL (OR 0.01 per 1 mmol/l, p=0.005), after logistic regression.\&\#10;Conclusions:\&\#10;Late onset autosomal dominant diabetes mellitus is clinically indistinguishable from classical type 2 diabetes individuals. However, LOADDM group is enriched for common HNF1A polymorphisms A98V and S487N. I27L showed "protective effect" upon hypertriglyceridemia in these sample of individuals, suggesting a role for HNF1A on diabetic individuals' lipid profile. These data contribute to the understanding of the complex interactions between genes, hyperglycemia and cardiovascular risk factors development in type 2 diabetes mellitus.}, author = {Giuffrida, Fernando and Furuzawa, Gilberto and Kasamatsu, Teresa and Oliveira, Marcos and Reis, Andre and Dib, Sergio}, citeulike-article-id = {4746391}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1475-2840-8-28}, doi = {10.1186/1475-2840-8-28}, issn = {1475-2840}, journal = {Cardiovascular Diabetology}, month = {June}, pages = {28+}, posted-at = {2009-06-04 17:40:23}, title = {HNF1A gene variants and cardiovascular risk factors in individuals with late-onset autosomal dominant diabetes: a cross-sectional study}, url = {http://dx.doi.org/10.1186/1475-2840-8-28}, volume = {8}, year = {2009} }

TY - JOUR ID - citeulike:4746391 L3 - citeulike-article-id:4746391 N2 - Background:
Type 2 diabetes mellitus (T2DM) is a genetically heterogeneous disease, hepatocyte nuclear factor-1 homeobox A (HNF1A) single-nucleotide polymorphisms (SNPs) playing a minor role in its pathogenesis. HNF1A is a frequent cause of monogenic diabetes, albeit with early-onset. Some uncommon subgroups like late-onset autosomal dominant diabetes mellitus (LOADDM) may present peculiar inheritance patterns with a stronger familial component. This study aims to investigate the relationship of HNF1A SNPs with cardiovascular risk factors in this group, as well as to characterize them in contrast with classical T2DM (CT2DM).
Methods:
eighteen LOADDM (age at onset > 40 y.o.; diabetes in 3 contiguous generations, uniparental lineage) along with 48 CT2DM patients and 42 normoglycemic controls (N group) have been evaluated for cardiovascular risk factors and SNPs of HNF1A.
Results:
LOADDM showed significantly higher frequencies of SNPs A98V (22.2% vs 2.1%, p=0.02) and S487N (72.2% vs 43.8%, p=0.049) of HNF1A compared to CT2DM. I27L did not show significant difference (66.7% vs 45.8%), but associated with lower risk of hypertriglyceridemia (OR 0.16, 95% CI 0.04-0.65, p=0.01). "Protective effect" was independent from other well-known predictive risk factors for hypertriglyceridemia, such as waist circumference (OR 1.09 per 1 cm increase, p=0.01) and HDL (OR 0.01 per 1 mmol/l, p=0.005), after logistic regression.
Conclusions:
Late onset autosomal dominant diabetes mellitus is clinically indistinguishable from classical type 2 diabetes individuals. However, LOADDM group is enriched for common HNF1A polymorphisms A98V and S487N. I27L showed "protective effect" upon hypertriglyceridemia in these sample of individuals, suggesting a role for HNF1A on diabetic individuals' lipid profile. These data contribute to the understanding of the complex interactions between genes, hyperglycemia and cardiovascular risk factors development in type 2 diabetes mellitus. JF - Cardiovascular Diabetology SN - 1475-2840 TI - HNF1A gene variants and cardiovascular risk factors in individuals with late-onset autosomal dominant diabetes: a cross-sectional study VL - 8 SP - 28 AU - Giuffrida, Fernando AU - Furuzawa, Gilberto AU - Kasamatsu, Teresa AU - Oliveira, Marcos AU - Reis, Andre AU - Dib, Sergio PY - 2009/06/02/ UR - http://dx.doi.org/10.1186/1475-2840-8-28 ER -