Uncertainty remains about the effects of perindopril on long-term morbidity and mortality in this clinical setting since this study had insufficient power for its primary endpoint. However, improved symptoms and exercise capacity and fewer hospitalizations for heart failure in the first year were observed on perindopril, during which most patients were on assigned therapy, suggesting that it may be of benefit in this patient population.

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina HumHap370 genotyping chips. In addition to strong association with the major histocompatibility complex (MHC; P < 10−800), we found association with SNPs in two gene deserts at 2p15 (rs10865331; combined P = 1.9 × 10−19) and 21q22 (rs2242944; P = 8.3 × 10−20), as well as in the genes ANTXR2 (rs4333130; P = 9.3 × 10−8) and IL1R2 (rs2310173; P = 4.8 × 10−7). We also replicated previously reported associations at IL23R (rs11209026; P = 9.1 × 10−14) and ERAP1 (rs27434; P = 5.3 × 10−12). This study reports four genetic loci associated with ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility.

Ž. Background: The prevalence of chronic heart failure CHF rises with increasing age, from -1% in those below 65 years of age to ) 5% in those over 65 years of age and is a major cause of morbidity and mortality in older people. Recent European guidelines point to a major deficiency in our knowledge of how to treat diastolic chronic heart failure, and a lack of information on treatment for heart failure in the elderly in general. Aims: The aims of this trial are to assess the potential benefits of the ACE inhibitor perindopril to treat chronic heart failure in elderly people, in the absence of any major left ventricular systolic dysfunction. Subjects: One thousand people over the age of 70 years will be recruited into this study. Evidence of chronic heart failure will be confirmed by clinical criteria and echocardiography. Methods: Once a diagnosis of chronic heart failure has been confirmed, the patient will receive either perindopril or placebo in addition to their usual treatment. Death, and unplanned heart failure related hospitalisations, are the primary outcomes. Quality of life, as measured by the Guyatt questionnaire will be assessed at the beginning of the study and at 1 year. Sub-studies of this trial include a Ž . 6-min walking test and more detailed evaluation of ventricular function as assessed by echocardiography . Both parameters will be measured at 8 weeks and 1 year, and analysed against baseline data. Cognitive function in this group of patients will also be evaluated at baseline and 1 year.