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J Hypertens DOI:10.1097/HJH.0b013e32835f5a83

Lack of interaction of beta-cell-function-associated variants with hypertension on change in fasting glucose and diabetes risk: the Framingham Offspring Study.

Publication TypeJournal Article
Year of Publication2013
Authorsde Miguel-Yanes, JM, Porneala, B, Pencina, MJ, Fox, CS, Florez, JC, Siscovick, DS, Dupuis, J, Meigs, JB
JournalJ Hypertens
Date Published2013 May
KeywordsAdult, 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 JournalJ. Hypertens.
PubMed ID23425704
PubMed Central IDPMC3745997
Grant ListR01 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