Coronary artery disease from a perspective of genomic risk score, ethical approaches and suggestions

As a leading cause of mortality, coronary artery disease is on the focus of genetic research as a complex trait. Although predictive genetic testing for cardiovascular diseases is on the counter, it is still hard to aggregate information from multiple genetic variants, environmental factors and family history into a single score. Every susceptibility allele provides small contribution to disease formation. Biomarkers play a role in various metabolic pathways. Genetic information and data depend heavily on probabilities. This should be clearly explained by genetic counselor to the patient and relatives who are looking for certain answers. Presence of susceptibility alleles can be a source of anxiety and it may result as a reduced self-confidence in ability to change health behavior. Complex diseases set a new stage to study novel techniques that can elucidate interactions among genetic, environmental and ethnic factors. The cookbook approach to treat a complex disease can often be misleading. Future studies may provide personalized information, which can improve the outcome of standardized treatments. As knowing one's own genetic risk is becoming a task for the responsible individual, it surely will add new challenges to ethical framework. Publicly marketing genetic tests for complex diseases raises ethical concerns. To avoid discriminatory use of genetic information; genetic risk scoring, therapeutic process, ethical policies must have a multifaceted progress. In this review, we summarized the attempts to resolve ethical issues related to genetic testing in complex diseases to resolve patient autonomy with individual responsibility and to aim the patient beneficence and confidentiality.     

Alu elements mediate large SPG11 gene rearrangements: further spatacsin mutations

PurposeHereditary spastic paraplegias compose a group of neurodegenerative disorders with a large clinical and genetic heterogeneity. Among the autosomal recessive forms, spastic paraplegia type 11 is the most common.MethodsTo better understand the spastic paraplegia type 11 mutation spectrum, we studied a group of 54 patients with hereditary spastic paraplegia. Mutation screening was performed by PCR amplification of SPG11 coding regions and intron boundaries, followed by sequencing. For the detection of large gene rearrangements, we performed multiplex ligation-dependent probe amplification.ResultsWe report 13 families with spastic paraplegia type 11 carrying either novel or previously identified mutations. We describe a complex entire SPG11 rearrangement and show that large gene rearrangements are frequent among patients with spastic paraplegia type 11. Moreover, we mapped the deletion breakpoints of three different large SPG11 deletions and provide evidence for Alu microhomology-mediated exon deletion.ConclusionOur analysis shows that the high number of repeated elements in SPG11 together with the presence of recombination hotspots and the high intrinsic instability of the 15q locus all contribute toward making this genomic region more prone to large gene rearrangements. These findings enlarge the amount of data relating repeated elements with neurodegenerative disorders and highlight their importance in human disease and genome evolution.     

Evaluation of cardiac autonomic function by various indices in patients with primary premature ovarian failure

Background

The association between premature ovarian failure (POF) and cardiovascular diseases (CVD) was investigated previously, but none of the studies have looked at cardiac autonomic functions in these patients. In this study, we aimed to evaluate cardiac autonomic functions in patients with POF.

Methods

We enrolled 26 female patients (mean age 37.5?±?10.1?years) with primary POF and 31 healthy subjects (mean age 37.5?±?9.0?years). All participants underwent 24-h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting 1st-, 2nd- and 3rd-min heart rates from maximal heart rate. Heart rate variability (HRV) and heart rate turbulence (HRT) parameters were analyzed in all patients.

Results

Both groups were similar with regard to age, gender, body mass index and left ventricular ejection fraction. Mean HRR1 (p?=?0.018), HRR2 (p?=?0.021) and HRR3 (p?=?0.027) values were significantly higher in the control group. When HRV considered SDNN, SDANN, RMSSD, PNN50 and HF were significantly decreased in patients with POF compared to healthy controls, but LF and LF/HF were significantly higher in POF patients. Both HRT onset and slope were more abnormal in POF patients. Also, there was a significant correlation between HRR, HRV and HRT parameters and FSH, LH and estradiol levels.

Conclusion

Our study results suggest that cardiac autonomic function is impaired in patients with POF despite the absence of overt cardiac involvement and symptoms. Further studies are needed to elucidate the prognostic significance and clinical implications of impaired autonomic functions in patients with POF.     

Serum caspase-9 levels are increased in patients with amyotrophic lateral sclerosis

It is known that apoptosis may play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). Moreover, caspase-9 is implicated in the apoptosis pathway. The aim of the study was to investigate caspase-9 levels in serum of patients with ALS. The study involved 30 patients with ALS and 30 patients from the control group. The serum caspase-9 levels were measured using the enzyme-linked immunosorbent method. The study showed that caspase-9 levels are significantly increased in serum of the patients with ALS comparing to the control group (p < 0.05). There was a significant correlation of serum caspase-9 levels with severity of clinical state of ALS patients and duration of the disease (p < 0.05). The results indicate that caspase-9 may be implicated in pathomechanism of neurodegeneration in ALS.