BackgroundIdentification of genetic markers of antihypertensive drug responses could assist in individualization of hypertension treatment.Methods and ResultsWe conducted a genome‐wide association study to identify gene loci influencing the responsiveness of 228 male patients to 4 classes of antihypertensive drugs. The Genetics of Drug Responsiveness in Essential Hypertension (GENRES) study is a double‐blind, placebo‐controlled cross‐over study where each subject received amlodipine, bisoprolol, hydrochlorothiazide, and losartan, each as a monotherapy, in a randomized order. Replication analyses were performed in 4 studies with patients of European ancestry (PEAR Study, N=386; GERA I and II Studies, N=196 and N=198; SOPHIA Study, N=372). We identified 3 single‐nucleotide polymorphisms within the ACY3 gene that showed associations with bisoprolol response reaching genome‐wide significance (P<5×10−8); however, this could not be replicated in the PEAR Study using atenolol. In addition, 39 single‐nucleotide polymorphisms showed P values of 10−5 to 10−7. The 20 top‐associated single‐nucleotide polymorphisms were different for each antihypertensive drug. None of these top single‐nucleotide polymorphisms co‐localized with the panel of >40 genes identified in genome‐wide association studies of hypertension. Replication analyses of GENRES results provided suggestive evidence for a missense variant (rs3814995) in the NPHS1 (nephrin) gene influencing losartan response, and for 2 variants influencing hydrochlorothiazide response, located within or close to the ALDH1A3 (rs3825926) and CLIC5 (rs321329) genes.ConclusionsThese data provide some evidence for a link between biology of the glomerular protein nephrin and antihypertensive action of angiotensin receptor antagonists and encourage additional studies on aldehyde dehydrogenase–mediated reactions in antihypertensive drug action.

Background Thiazide diuretics have been recommended as a first-line antihypertensive treatment, although the choice of ‘the right drug in the individual essential hypertensive patient’ remains still empirical. Essential hypertension is a complex, polygenic disease derived from the interaction of patient’s genetic background with the environment. Pharmacogenomics could be a useful tool to pinpoint gene variants involved in antihypertensive drug response, thus optimizing therapeutic advantages and minimizing side effects. Methods and results We looked for variants associated with blood pressure response to hydrochlorothiazide over an 8-week follow-up by means of a genome-wide association analysis in two Italian cohorts of never-treated essential hypertensive patients: 343 samples from Sardinia and 142 from Milan. TET2 and CSMD1 as plausible candidate genes to affect SBP response to hydrochlorothiazide were identified. The specificity of our findings for hydrochlorothiazide was confirmed in an independent cohort of essential hypertensive patients treated with losartan. Our best findings were also tested for replication in four independent hypertensive samples of European Ancestry, such as GENetics of drug RESponsiveness in essential hypertension, Genetic Epidemiology of Responses to Antihypertensives, NORdic DILtiazem intervention, Pharmacogenomics Evaluation of Antihypertensive Responses, and Campania Salute Network-StayOnDiur. We validated a polymorphism in CSMD1 and UGGT2. Conclusion This exploratory study reports two plausible loci associated with SBP response to hydrochlorothiazide: TET2, an aldosterone-responsive mediator of αENaC gene transcription; and CSMD1, previously described as associated with hypertension in a case–control study.

Objective. To provide new evidence on whether and how patterns of health care utilization deviate from horizontal equity in a country with a universal and egalitarian public health care system: Italy. Data Sources. Secondary analysis of data from the Health Conditions and Health Care Utilization Survey 2005, conducted by the Italian National Institute of Statistics on a probability sample of the noninstitutionalized Italian population. Study Design. Using multilevel logistic regression, we investigated how the probability of utilizing five health care services varies among individuals with equal health status but different SES. Data Collection/Extraction. Respondents aged 18 or older at the interview time (n = 103,651). Principal Findings. Overall, we found that use of primary care is inequitable in favor of the less well-off, hospitalization is equitable, and use of outpatient specialist care, basic medical tests, and diagnostic services is inequitable in favor of the well-off. Stratifying the analysis by health status, however, we found that the degree of inequity varies according to health status. Conclusions. Despite its universal and egalitarian public health care system, Italy exhibits a significant degree of SES-related horizontal inequity in health services utilization.

Personalised health care is an evolution, moving away from a disease-focused model of care, translating scientific and technological advances into benefits for patients, and placing them at the centre of the patients' health and care. Companion diagnostics emerge as a very specific and special group of in vitro diagnostics among the different technologies shaping the personalised health care spectrum. Companion diagnostics provide highly valuable information, allowing patients, health practitioners and payers to decide with a higher level of certainty on the potential benefits of a treatment or care pathway. Decreasing uncertainty may result in a more efficient selection of treatments and care, targeted at subpopulations that are most likely to benefit. Companion diagnostics account for a minimal portion of the already small expenditure on in vitro diagnostics (far less than 1% of total health care expenditure), and yet they provide the means to limit inefficient use of health care resources while optimising patient outcomes. It is clear that equal access to personalised health care is still an issue across the EU. One of the most common perceived barriers is affordability. The investment in companion diagnostics can provide long-term value for patients and health care systems, shifting resources to areas of need. Health systems do not fully recognise yet the value that companion diagnostics bring to make personalised health care more affordable across the EU. This inhibits patient access to personalised treatments and care, preventing improved outcomes. In many countries, market access frameworks for diagnostic tests are fragmented and not aligned with specific funding and reimbursement mechanisms, discouraging the use of these tests. Emerging evidence shows that patients are missing out on the appropriate tests and treatments while a reduction in the inefficient use of health care resources is not realised. This article outlines some of these market access barriers for companion diagnostics in the EU, including reimbursement challenges specific to some member states (Germany, the UK, and France). Furthermore, proposals addressing barriers and increasing timely patient access to companion diagnostics in the EU are presented.

Using a genome-wide approach, we identified the CAMK1D gene as a novel locus associated with blood pressure response to losartan. CAMK1D gene characterization may represent a useful tool to personalize the treatment of essential hypertension.