Algemene verordening gegevensbescherming : Vriend of vijand van onderzoekers?

As of May 2018, the use of personal data in medical research is regulated under the General Data Protection Regulation (GDPR). While, as before, in principle patients’ consent for the use of their personal data is still required, exemptions for medical research still exist. When all of the criteria for the exemptions are met, and the other requirements of the GDPR are adhered to, personal data can be used in medical research without consent. In this paper we present a brief outline of a number of GDPR-related requirements for use of personal data in medical research. Furthermore, we discuss how GDPR interlinks with the Medical Research Involving Human Subjects Act (WMO) and in which areas GDPR remains subject to interpretation. Medical researchers using personal data need to be aware when consent is required and on which grounds personal data can be used without consent in the Netherlands

Algemene Verordening Gegevensbescherming

As of May 2018, the use of personal data in medical research is regulated under the General Data Protection Regulation (GDPR). While, as before, in principle patients' consent for the use of their personal data is still required, exemptions for medical research still exist. When all of the criteria for the exemptions are met, and the other requirements of the GDPR are adhered to, personal data can be used in medical research without consent. In this paper we present a brief outline of a number of GDPR-related requirements for use of personal data in medical research. Furthermore, we discuss how GDPR interlinks with the Medical Research Involving Human Subjects Act (WMO) and in which areas GDPR remains subject to interpretation. Medical researchers using personal data need to be aware when consent is required and on which grounds personal data can be used without consent in the Netherlands

Algemene verordening gegevensbescherming : Vriend of vijand van onderzoekers?

As of May 2018, the use of personal data in medical research is regulated under the General Data Protection Regulation (GDPR). While, as before, in principle patients’ consent for the use of their personal data is still required, exemptions for medical research still exist. When all of the criteria for the exemptions are met, and the other requirements of the GDPR are adhered to, personal data can be used in medical research without consent. In this paper we present a brief outline of a number of GDPR-related requirements for use of personal data in medical research. Furthermore, we discuss how GDPR interlinks with the Medical Research Involving Human Subjects Act (WMO) and in which areas GDPR remains subject to interpretation. Medical researchers using personal data need to be aware when consent is required and on which grounds personal data can be used without consent in the Netherlands

Congenital atrial standstill associated with coinheritance of a novel SCN5A mutation and connexin 40 polymorphisms

The novel SCN5A mutation L212P was identified in the proband (age 11 years) and his father. The father was in normal sinus rhythm. The proband had no P waves on surface ECG, and his right atrium could not be captured by pacing. The recombinant L212P Na channel showed a large hyperpolarizing shift in both the voltage dependence of activation (WT: −48.1 ± 0.9 mV; L212P: −63.5 ± 1.5 mV; P < .001) and inactivation (WT: −86.6 ± 0.9 mV; L212P: −95.6 ± 0.8 mV; P < .001) and delayed recovery from inactivation. Further screenings for genetic variations that might mitigate L212P dysfunction revealed that the proband, but not his father, carries Cx40 polymorphisms inherited from his asymptomatic mother

Polymorphisms in human connexin40 gene promoter are associated with increased risk of hypertension in men

OBJECTIVE: Gap junctions, formed by connexins (Cx), are important in the regulation of vascular tone. Previously, we reported two closely linked polymorphisms (-44G --> A and +71A --> G) within regulatory regions of the gene for Cx40, a major connexin in the vascular wall and the kidney. In the present study, we examined the hypothesis that these polymorphic variants are associated with hypertension and that they interact with blood pressure in healthy individuals. METHODS: Cx40 genotypes were determined in 191 subjects with essential hypertension, 198 normotensive individuals, and a healthy control population (178 twin pairs, 108 monozygotic, 70 dizygotic). RESULTS: We found a significant contribution of the minor Cx40 allele or genotype (-44AA/+71GG) to the risk of hypertension in men (P = 0.013 or P = 0.035; odds ratio, 1.87 or 2.10, respectively), but not in women. Moreover, in the healthy control population a significant effect of Cx40 genotype and sex on systolic blood pressure was found (P < 0.05 and P < 0.0001, respectively). Women carrying the minor Cx40 genotype had significantly higher systolic blood pressure compared with non-carriers (P < 0.05). In men, systolic blood pressure in carriers of the minor Cx40 genotype was not significantly different from the other two genotypes, possibly because of the small number of men in this group. However, men carrying the -44GA/+71AG genotype had higher standing systolic blood pressure compared with the more common Cx40 genotype (-44GG; P = 0.033). CONCLUSION: These findings suggest that the Cx40 polymorphisms may form a genetic susceptibility factor for essential hypertension in me

Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system

Cardiac conduction defects associate with mutations in SCN5A, the gene encoding the cardiac Na+ channel. In the present study, we characterized a family in which the proband was born in severe distress with irregular wide complex tachycardia. His older sister died at 1 year of age from severe conduction disease with similarly widened QRS-complexes. Mutational analysis of SCN5A in the proband demonstrated compound heterozygosity for a nonsense mutation (W156X), inherited from the father, and a missense mutation (R225W), inherited from the mother. Genotyping on DNA extracted from tissue from the deceased sibling revealed the same SCN5A genotype. Injection of cRNA encoding the W156X mutation in Xenopus oocytes did not produce any current. The R225W substitution neutralizes the third Arg residue within the voltage-sensing segment of domain I. Expression studies showed that this mutation leads to a severe reduction in I-Na and is also associated with gating changes. Histological examination of the heart from the deceased sibling revealed changes consistent with a dilated type of cardiomyopathy and severe degenerative abnormalities of the specialized conduction system. The occurrence of compound heterozygosity for these two mutations implies that the proband carries solely severely dysfunctional cardiac Na+ channels. This explains his severe phenotype and that of his deceased sister who had been a carrier of the same genotype. The morphological changes within the heart of the deceased sibling may have occurred secondary to the Na+ channel abnormality and contributed to the severity of the disorder in this individua

Heterogeneous Connexin43 distribution in heart failure is associated with dispersed conduction and enhanced susceptibility to ventricular arrhythmias

Aims Sudden arrhythmogenic cardiac death is a major cause of mortality in patients with congestive heart failure (CHF). To investigate determinants of the increased arrhythmogenic susceptibility, we studied cardiac remodelling and arrhythmogenicity in CHF patients and in a mouse model of chronic pressure overload. Methods and results Clinical and (immuno) histological data of myocardial biopsies from CHF patients with (VT+) and without (VT-) documented ventricular arrhythmia were compared with controls. In CHF patients, ejection fraction was decreased and QRS duration was increased. Cell size and interstitial fibrosis were increased, but Connexin43 (Cx43) levels, the most abundant gap junction in ventricular myocardium, were unchanged. No differences were found between VT+ and VT- patients, except for the distribution pattern of Cx43, which was significantly more heterogeneous in VT+. Mice were subjected to transverse aortic constriction (TAC) or sham operated. At 16 weeks, cardiac function was determined by echocardiography and epicardial ventricular activation mapping was performed. Transverse aortic constriction mice had decreased fractional shortening and prolonged QRS duration. Right ventricular conduction velocity was reduced, and polymorphic VTs were induced in 44% TAC and 0% sham mice. Interstitial fibrosis was increased and Cx43 quantity was unchanged in TAC mice with and without arrhythmias. Similar to CHF patients, heterogeneous Cx43 distribution was significantly associated with arrhythmias in TAC mice and with spatial heterogeneity of impulse conduction. Conclusion Heterogeneous Cx43 expression during CHF is associated with dispersed impulse conduction and may underlie enhanced susceptibility to ventricular tachyarrhythmia