J. B. Richards

Homocysteine levels and leukocyte telomere length

OBJECTIVE Elevated plasma homocysteine is a risk factor for vascular diseases, possibly due to homocysteine-mediated increase in oxidative stress and inflammation. As leukocyte telomere length (LTL) registers the cumulative oxidative stress and inflammation, we examined the relationship between homocysteine and LTL. METHODS LTL was measured using the Southern blot method. The relationship between LTL and homocysteine levels was considered for confounding with the following covariates: age, sex, smoking, obesity, physical activity, menopause, hormone replacement therapy use and creatinine clearance. RESULTS 1,319 healthy subjects were recruited from a population-based cohort. LTL was negatively correlated with plasma homocysteine levels, after adjustment for smoking, obesity, physical activity, menopause, hormone replacement therapy use and creatinine clearance. The difference in multiply-adjusted LTL between the highest and lowest tertile of homocysteine levels was 111 base pairs (p=0.004), corresponding to 6.0 years of telomeric aging. This relationship was further accentuated by decreased concentrations of serum folate and increased levels of C-reactive protein. CONCLUSIONS Increased homocysteine levels are associated with shortened LTL, further supporting the tenet that LTL is an index of cardiovascular risk.

A genome-wide association study identifies a novel locus on chromosome 18q12.2 influencing white cell telomere length

Background: Telomere length is a predictor for a number of common age related diseases and is a heritable trait. Methods and results: To identify new loci associated with mean leukocyte telomere length we conducted a genome wide association study of 314 075 single nucleotide polymorphisms (SNPs) and validated the results in a second cohort (n for both cohorts combined  =  2790). We identified two novel associated variants (rs2162440, p = 2.6×10−6; and rs7235755, p = 5.5×10−6) on chromosome 18q12.2 in the same region as the VPS34/PIKC3C gene, which has been directly implicated in the pathway controlling telomere length variation in yeast. Conclusion: These results provide new insights into the pathways regulating telomere homeostasis in humans.

An analysis of which anti-osteoporosis therapeutic regimen would improve compliance in a population of elderly adults.

ABSTRACT Objective: Although medications to prevent osteoporotic fractures have been proven to be effective, compliance to these therapies is generally poor. Therapeutic regimens for different anti-osteoporotic medications differ widely and it is currently unknown which regimen would be most preferred by patients. Research design and methods: We conducted a large, population-based study to discern which therapeutic attributes would be most preferable to a population representative of the age and sex distribution of patients with osteoporosis. Results: Our study sample was restricted to persons aged 55 years and over and comprised 2485 individuals (mean age of 64.5 years). The study population was predominantly female (90.3%) and two-thirds of the respondents reported current daily medication use. Nearly half (45%) of the study population preferred to take medications daily, while one in five preferred weekly therapy and 30% preferred monthly therapy ( p < 0.0001 for between proportion comparisons). When given the option of choosing between three different medication regimen scenarios, those subjects not currently using anti-osteoporotic medications preferred a theoretical regimen which was daily and did not involve subsequent fasting and maintaining an upright posture. Conclusions: Our data suggest that compliance with osteoporotic medications could be improved if patients are able to choose a therapeutic regimen best suited to their particular needs. The majority of subjects preferred a drug which was taken daily and with minimal inconvenience, rather than a weekly drug with slightly more inconvenience. Given that most physicians currently prescribe anti-osteoporotic therapy as a weekly regimen, at the time of diagnosis physicians should ascertain which regimen would be most preferable to patients prior to initiating therapy.