A Kinesin Family Member 6 Variant Is Associated With Coronary Heart Disease in the Women’s Health Study

ObjectivesWe asked if carriers of the 719Arg allele of kinesin family member 6 (KIF6) have increased risk of coronary heart disease (CHD) in a cohort of initially healthy Caucasian American women.BackgroundThe 719Arg allele of KIF6 (rs20455) has been reported to be associated with increased risk of CHD in a large population-based prospective study, ARIC (Atherosclerosis Risk in Communities), and in the placebo arms of 2 statin trials, CARE (Cholesterol and Recurrent Events) and WOSCOPS (West of Scotland Coronary Prevention Study). However, this KIF6 variant was not specifically investigated in the female subgroup in the ARIC study, and the CARE and WOSCOPS trials included only a small number of female patients.MethodsGenotypes of the rs20455 single nucleotide polymorphism (SNP) were determined among 25,283 initially healthy Caucasian women, age 45 years and older, participating in the WHS (Women’s Health Study) who were prospectively followed over a 12-year period for incident cardiovascular events. The risk associated with the 719Arg allele of KIF6 was estimated using Cox proportional hazards models that adjusted for age and traditional risk factors.ResultsDuring follow-up, 953 women suffered a first-ever CHD event (myocardial infarction, coronary revascularization, or cardiovascular death) or first-ever ischemic stroke. Compared with noncarriers, carriers of the 719Arg allele had an increased risk of CHD (hazard ratio [HR] = 1.24 [95% confidence interval (CI) 1.04 to 1.46, p = 0.013]) and myocardial infarction (HR = 1.34 [95% CI 1.02 to 1.75, p = 0.034]) but not ischemic stroke.ConclusionsConfirming and extending previous reports, carriers of the 719Arg allele of KIF6 have 34% higher risk of myocardial infarction and 24% higher risk of CHD compared with noncarriers among 25,283 women from the WHS

Association analyses of RFLPs for the α2- and β1-adrenoceptor genes in essential hypertension

Adrenoceptor stimulation has an important role in normal cardiovascular regulation and a genetic defect could be a cause of essential hypertension (HT). The present study examined the relationship with HT of RFLPs for the α2-adrenoceptor gene (ADRA2R) and β1-adrenoceptor gene (ADRB1R), which share the same chromosomal locus (10q24-26). Subjects were HTs and normotensives (NTs) whose parents had a similar blood pressure status at age ≥ 50. The frequency of the minor allele of the DraI RFLP of ADRA2R was 0.17 in HTs (n = 76) and 0.17 in NTs (n = 87). For the BglI RFLP of ADRBIR, frequency of the minor allele was 0.10 in HTs (n = 62) and 0.12 in NTs (n = 88). χ2 analysis showed no difference between HT and NT groups. Thus the present study provides no basis for involvement of the α2- or β1-adrenoceptor genes in essential hypertension.</p

Mean leukocyte telomere length and risk of incident colorectal carcinoma in women: a prospective, nested case-control study

Background: To date, no prospective epidemiological data are available, particularly in women, on mean leukocyte telomere length as a risk predictor. Methods: Using leukocyte DNA samples collected at baseline in a prospective cohort of over 28,000 initially healthy women, we examined the relationship between mean leukocyte telomere repeat copy number to single gene copy number (TSR) in 134 incident cases of colorectal carcinoma (CRC), and 357 matched controls; all were Caucasian. Results: The observed loge-transformed TSRs were similar between cases and controls (p=0.79). Using an adjusted analysis, we found no evidence for an association of the loge-TSRs with CRC risk [adjusted odds ratio (OR)=0.943, 95% confidence interval (CI)=0.647–1.376, p=0.762]. Stratified analysis by median follow-up time, or postmenopausal status also showed similar null findings. Conclusions: In concordance with our previous findings in Caucasian men, the present study in Caucasian women found no evidence for an association of mean leukocyte telomere length with risk of incident CRC, further suggesting that leukocyte telomere length may not be a useful indicator for risk assessment. Clin Chem Lab Med 2010;48:259–62.Peer Reviewe