|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||de Miguel-Yanes, JM, Porneala, B, Pencina, MJ, Fox, CS, Florez, JC, Siscovick, DS, Dupuis, J, Meigs, JB|
|Date Published||2013 May|
|Keywords||Adult, Blood Glucose, Diabetes Mellitus, Type 2, Fasting, Female, Humans, Hypertension, Insulin-Secreting Cells, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors|
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.
METHODS AND 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
CONCLUSION: 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.
|Alternate Journal||J. Hypertens.|
|PubMed Central ID||PMC3745997|
|Grant List||R01 DK078616 / DK / NIDDK NIH HHS / United States |
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
K24 DK080140 / DK / NIDDK NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States