The genetic background of Parkinson's disease: current progress and future prospects.

Almost two decades of genetic research in Parkinson's disease (PD) have remarkably increased our knowledge regarding the genetic basis of PD with numerous genes and genetic loci having been found to cause familial PD or affect the risk for PD. Approximately 5-10% of PD patients have monogenic forms of the disease, exhibiting a classical Mendelian type of inheritance, however, the majority PD cases are sporadic, probably caused by a combination of genetic and environmental risk factors. Nowadays, six genes, alpha synuclein, LRRK2, VPS35, Parkin, PINK1 and DJ-1, have definitely been associated with an autosomal dominant or recessive PD mode of inheritance. The advent of genome-wide association studies (GWAS) and the implementation of new technologies, like next generation sequencing (NGS) and exome sequencing has undoubtedly greatly aided the identification on novel risk variants for sporadic PD. In this review, we will summarize the current progress and future prospects in the field of PD genetics.

Apelin and G212A apelin receptor gene polymorphism in obese and diabese youth.

OBJECTIVE: The apelinergic system has been previously described to participate in fluid homeostasis, cardiac contractility, blood pressure and neo-vascularization. The role of apelin in obesity and glucose metabolism has also lately gained interest; however, it still remains obscure. This study aimed to assess serum apelin levels in obese youngsters and to investigate any possible association with the G212A polymorphism of the apelin receptor (APLNR) gene. METHODS: Ninety obese individuals and 90 matched for age and gender lean controls were included. Anthropometric measurements, data of glucose metabolism, including an oral glucose tolerance test, and serum apelin levels were obtained. The presence of the G212A polymorphism of the APLNR gene was also analyzed in the obese group. RESULTS: Obese participants had significantly lower serum apelin levels as compared with controls (P = 0.011). After being grouped according to their status of glucose metabolism, only obese subjects with impaired glucose metabolism (diabese) exhibited lower apelin levels as compared with controls. The presence of the G212A polymorphism did not differ from the HapMap-reported frequencies in Caucasians (GG = 53.3%/GA = 38.9%/ΑΑ = 7.8% vs. GG = 46.9%/GA = 39.8%/ΑΑ = 13.3%, P = 0.232). The GG and GA obese subgroups had significantly lower apelin levels as compared with the AA group (P = 0.013 and P = 0.016, respectively). CONCLUSION: Obese (especially diabese) youngsters demonstrated lower serum apelin levels; the G212A polymorphism of the APLNR gene was found to exert a favourable effect on circulating apelin levels in childhood obesity.

Glutathion-S-Transferase P1 polymorphisms association with broncopulmonary dysplasia in preterm infants.

BACKGROUND: Oxidative stress, characterized by the excretion of pre-oxidative and anti-oxidative proteases, has a key role in the pathogenesis of bronchopulmonary dysplasia (BPD). One of the many host anti-oxidant enzymes is glutathione-S-transferase P1 (GSTP1), with three polymorphic alleles having been identified: homozygous ile, heterozygous ile/val and homozygous val isomorph. The aim of this study was to examine the genetic predisposition to BPD in the GSTP1 polymorphisms. METHODS: A prospective case-control study was carried out in the 2nd Neonatal Intensive Care Unit of Aristotle University in Thessaloniki, Greece during 2008. The genetic polymorphisms of GSTP1 in 28 preterms <32 weeks gestational age (GA) with BPD compared to 74 controls (33 preterms without BPD and 41 healthy terms) were examined. RESULTS: The homozygous ile isomorph was predominant in all groups (preterms with BPD: 82%, preterms without BPD: 70%, healthy terms: 78%), followed by the heterozygous ile/val (14%, 18% and 20% respectively) and the homozygous val isomorph (4%, 12% and 2% respectively). The homozygous ile isomorph was also identified in the majority of preterms with mild (80%), moderate (100%) and severe (73%) BPD. The GSTP1 genetic distribution did not differ between the groups and GSTP1 polymorphisms were not associated with the severity of BPD. CONCLUSIONS: This study could not confirm an association between GSTP1 polymorphisms and the development of BPD or the severity of the disease.

Pharmacological treatment and the prospect of pharmacogenetics in Parkinson's disease.

Parkinson disease (PD) is a progressive movement disorder marked by tremor, rigidity, bradykinesia and postural instability. Levodopa (l-dopa), usually combined with a peripheral dopa decarboxylase inhibitor, has been proved to provide the best symptomatic benefit for PD. However, its long-term efficacy is limited because of motor complications and drug-induced dyskinesia. Dopamine agonists, catechol-O-methyltransferase inhibitors and monoamine oxidase-B inhibitors are anti-parkinsonian (anti-PD) drugs that have been found to further improve the potency of l-dopa and prevent the onset of motor complications. However, as PD is a progressive disorder, all the drugs used for its therapy, manifest reduced efficacy and adverse effects with time. Research on the field of pharmacogenetics has pointed out that the genetic variability of each individual determines to a large extent the inter-individual variability in response to anti-PD drugs. Clinicogenetic trials show that drug efficacy or toxicity or susceptibility to side effects are features governed by genetic principles. This article is a review of the present pharmacological treatment of PD and current pharmacogenetic data for PD.

The G2019S LRRK2 mutation is uncommon amongst Greek patients with sporadic Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting approximately 2% of the population >60 years of age. Although, the etiology of PD is still unknown, the genetic background of the disease has been documented. Recently, a mutation in the LRRK2 gene, G2019S, was associated with 3-41% and 1-2% of familial and sporadic PD, respectively suggesting a pivotal role of LRRK2 in PD. In this report, we examine the association of the G2019S mutation with sporadic late-onset PD, in an independent cohort of Greek patients and controls.