title: HNF1A gene polymorphisms and cardiovascular risk factors in individuals with late-onset autosomal dominant diabetes: a cross-sectional study.
abstract: 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 this 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.
authors.affiliation: Universidade Federal de São Paulo, Departamento de Medicina, Disciplina de Endocrinologia, R, Pedro de Toledo, 981 12o andar, Vila Clementino, Sao Paulo, SP - Brazil. fernandogiuffrida@uol.com.br
authors.forename: Fernando M A
authors.initials: FM
authors.lastname: Giuffrida
authors.forename: Gilberto K
authors.initials: GK
authors.lastname: Furuzawa
authors.forename: Teresa S
authors.initials: TS
authors.lastname: Kasamatsu
authors.forename: Marcos M
authors.initials: MM
authors.lastname: Oliveira
authors.forename: Andre F
authors.initials: AF
authors.lastname: Reis
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Dib
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000145:classification / Q000150:complications* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha