Kcnmb1 Genotype Associated With Cardiovascular Outcomes In The International Verapamil Sr/Trandolapril Study (Invest).

BACKGROUND Glu65Lys in KCNMB1 has been found to have functional and clinical significance. We tested whether Glu65Lys or Val110Leu were associated with cardiovascular (CV) outcomes (death, nonfatal myocardial infarction (MI) or nonfatal stroke) in a substudy of INVEST. METHODS INVEST studied patients with HTN and CAD randomized to verapamil SR- or atenolol-based treatment strategies. Codons 65 and 110 were genotyped in 271 cases and 813 age, sex, and race-matched controls from the genetic cohort. Age, sex, BMI, baseline BP, race, ACE inhibitor use, diuretic use, previous MI or stroke, history of heart failure (HF) or diabetes (DM), genotype (Lys 65 or Leu 110 carrier status), treatment strategy, and interaction between strategy and genotype were included in logistic regression analysis. RESULTS Odds ratios for all significant parameters are shown in the table. Lower BMI, history of DM or HF, and higher SBP at baseline were all associated with an increased risk of CV outcome. ACE inhibitor and diuretic use were associated with a decreased risk. Individuals with the Val110Val genotype had an increased risk of CV outcome compared to Leu110 carriers. The interaction between treatment and genotype was not significant. Variable Odds Ratio 95% Confidence Interval Val110Val 1.585 1.021–2.461 ACE use 0.537 0.38–0.756 Diuretic use 0.573 0.416–0.810 SBP (per 1 mm Hg) 1.014 1.006–1.021 BMI (per 1 kg/m2) 0.936 0.907–0.965 DM 2.03 1.46–2.80 HF 2.57 1.46–4.55 CONCLUSIONS These data suggest that in addition to traditional risk factors, the Val110Val genotype may be associated with an increased risk of death, nonfatal MI or stroke. This genetic effect was not influenced by treatment strategy, and Glu65Leu did not influence outcomes. Clinical Pharmacology & Therapeutics (2005) 79, P41–P41; doi: 10.1016/j.clpt.2005.12.144