title: Lack of interaction of beta-cell-function-associated variants with hypertension on change in fasting glucose and diabetes risk: the Framingham Offspring Study.
abstract: OBJECTIVE
  To test whether pancreatic beta-cell genetic frailty and hypertension (HTN) interact in their associations with change over time in fasting glucose (ΔFG) or type 2 diabetes mellitus (T2D) risk.
  
  
  RESULTS
  We pooled data from 3471 Framingham Offspring Study participants into six ∼4-year periods (15 852 person-examinations; mean age 52; 54% women). We defined two genetic exposures reflecting beta-cell genetic risk burden: single nucleotide polymorphism (SNP) score counts of fasting glucose-associated and T2D-associated risk alleles at 16 and 33 putative beta-cell loci, respectively; and three HTN exposures: HTN versus no-HTN; treated versus untreated HTN; and five mutually exclusive antihypertensive categories (beta-blockers, thiazides, renin-angiotensin system agents, combinations, others) versus untreated HTN. We tested ∼4-year mean ΔFG or odds of T2D by per-risk allele score change and HTN category, seeking genetic score-by-HTN interaction. Genetic scores increased ∼4-year ΔFG (0.6  mg/dl per-risk allele; P = 8.9 × 10(-16)) and T2D-risk (∼17% per-risk allele; P = 2.1 × 10(-7)). As compared to no-HTN, HTN conferred higher ΔFG (2.6 versus 1.7 mg/dl; P < 0.0001) and T2D-risk [odds ratio (OR) = 2.9, 95% confidence interval (CI) 2.8-3.0; P < 0.0001]. As compared to untreated HTN, treated HTN conferred higher ΔFG (3.4 versus 3.0 mg/dl; P < 0.0001) and T2D-risk (OR = 1.4, 95% CI 1.3-1.5; P = 0.02). Beta-blockers (OR = 1.6, 95% CI 1.1-2.4), combinations (OR = 1.6, 95% CI 1.1-2.5), and others (OR = 2.0, 95% CI 1.4-2.9) increased T2D-risk (all P < 0.02). In joint models including interaction terms, all genetic score-by-HTN interaction terms were P value greater than 0.05. In joint models without interaction, fasting glucose-SNP or T2D-SNP genetic scores (both P < 0.001) and HTN (P < 0.0001) independently increased ΔFG or T2D-risk.
  
  
  CONCLUSIONS
  HTN, HTN treatment, and common fasting glucose-SNP genetic score/T2D-SNP genetic score independently predicted ΔFG and T2D incidence, but did not modify each other's association with ΔFG or T2D risk.
authors: Hospital Gregorio Marañón, Universidad Complutense de Madrid, and Hospital del Sureste, Madrid, Spain.
authors: Jose M
authors: JM
authors: de Miguel-Yanes
authors: Bianca
authors: B
authors: Porneala
authors: Michael J
authors: MJ
authors: Pencina
authors: Caroline S
authors: CS
authors: Fox
authors: Jose C
authors: JC
authors: Florez
authors: David S
authors: DS
authors: Siscovick
authors: Josée
authors: J
authors: Dupuis
authors: James B
authors: JB
authors: Meigs
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000235:genetics; D005215:Fasting / Q000097:blood*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D001786:Blood Glucose