Association of Genetic Polymorphisms in Kawasaki Disease with the Response to Intravenous Immunoglobulin Therapy.

Kawasaki disease (KD) is an acute febrile and systemic vasculitis disease mainly affecting children < 5 years old. Although the first case of KD was reported in 1967 and despite extensive research on KD since then, the cause of the disease remains largely unknown. The most common complications of KD are coronary artery lesions (CAL), which significantly increase the risk of coronary heart disease. The standard treatment for KD is high-dose intravenous immunoglobulin (IVIG) plus aspirin within 10 days from symptoms' appearance, which has been shown to decrease the incidence of CAL to 5-7%. Despite the benefits of IVIG, about 25% of the patients treated with IVIG develop resistance or are unresponsive to the therapy, which represents an important risk factor for CAL development. The cause of IVIG unresponsiveness has not been fully elucidated. However, the role of gene polymorphisms in IVIG response has been suggested. Herein, we comprehensively review genetic polymorphisms in KD that have been associated with IVIG resistance/unresponsiveness and further discuss available models to predict IVIG unresponsiveness.Kindly check and confirm inserted city in affiliation [1] is correctly identified.confirm.

Association of NFKB1, NKX2-5, GATA4 and RANKL Gene Polymorphisms with Sporadic Congenital Heart Disease in Greek Patients.

Congenital heart disease (CHD) is a group of structural defects of the heart and the great vessels, and one of the leading causes of death among infants and young adults. Several gene variants are involved in diverse mechanisms of cardiac and vessel development and could thus be considered candidate mutated genes for a congenital heart defect or a specific variant could predispose a person to CHD. In the present study, variants in four such genes are investigated for the first time in a group of young Greek CHD patients: the NFKB1 gene polymorphism (-94ins/ delATTG), rs28362491, NKX2-5 gene polymorphism rs2277923, GATA4 gene polymorphism rs11785481 and RANKL gene polymorphism rs4531631. A total of 43 CHD patients and 100 healthy adults were included in the study. The polymerase chain reaction-restriction fragment length polymorphism (PRC-RFLP) method was used to genotype the aforementioned polymorphisms of NFKB1, NKX2-5, GATA4 and RANKL. The association analysis identified that there was a protective association between CHD and the A allele of rs2277923 polymorphism (p = 0.004). The D allele of the rs28362491 polymorphism is also a likely risk factor for causing CHD (p = 0.006). The differences of the rs4531631 and rs11785481 variant contribution had no statistical significance between the groups (p >0.05). In conclusion, our results revealed that the rs28362491 and rs2277923 gene polymorphisms, but not the rs4531631 and rs11785481 polymorphisms, may contribute to CHD risk in a cohort of Greek CHD patients.

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.

A 2-year prospective densitometric study on the influence of Fok-I gene polymorphism in young patients with thalassaemia major.

UNLABELLED: This study is to estimate the degree of genetic contribution of Fok-I gene polymorphism of Vitamin D receptor to bone mass in patients with thalassaemia. Results indicate a protective role of the f allele of the Fok-I gene polymorphism when found in homozygosity on bone mineral density of young thalassemic patients. INTRODUCTION: The purpose of this study is to estimate prospectively the degree of genetic contribution of Fok-I gene polymorphism of vitamin D receptor (VDR) to the evolution of bone mass in patients with beta-thalassemia major (b-TH). METHODS: Sixty-four children and young adults (33 males and 31 females) with mean decimal age of 23.20 ± 5.41 (range 9.25-32.41 years) were recruited in this study. All patients were genotyping for Fok-I gene polymorphism and were assessed with dual energy X-ray absorptiometry (DXA) at baseline and 2 years after. Z-scores were calculated based on normal age and sex matched Caucasian population. Metabolites of vitamin D, intact PTH, total calcium, inorganic phosphorous, and alkaline phosphatase were measured at the serum pre-transfusion. RESULTS: A moderate proportion of patients had decreased DXA Z-scores (Z-score ≤-2) predominately in total hip (31 %) and secondary in lumbar spine (15.6 %). Patients being homozygous for the f allele had apparently higher BMD Z-scores compared with those carrying the F allele in homo- or heterozygosity, however, with a difference that did not reached significance. Interestingly enough, a significant deterioration in BMD Z-scores measured at femur (FF: P = 0.004 Ff: P < 0.001, ff: P = 0.024) and total hip (FF: P = 0.022, Ff: P = 0.005) was recorded for all type of genotypes, except for ff genotype and with regard to the total hip DXA values. An increased prevalence of serum 25(OH)D3 deficiency (59.4 %) and 25(OH)D3 borderline (12.5 %) was recorded. CONCLUSION: Our study indicates a protective role of the f allele of the Fok-I gene polymorphism when found in homozygosity on bone mineral density of young patients with b-TM.

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.

Identification of a mutation in the MTM1 gene, associated with X-linked myotubular myopathy, in a Greek family.

X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy, usually characterized by severe hypotonia and respiratory insufficiency at birth, in affected, male infants. The disease is causally associated with mutations in the MTM1 gene, coding for phosphatase myotubularin. We report a severe case of XLMTM with a novel mutation, at a donor splicing site (c.1467+1G) previously associated with severe phenotype. The mutation was also identified in the patient's mother, providing an opportunity for sound genetic counseling.

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.

Association of phosphodiesterase 4D gene G0 haplotype and ischaemic stroke in a Greek population.

We have examined the association of phosphodiesterase 4D (PDE4D) single nucleotide polymorphism (SNP45) and microsatellite marker AC008818-1 with ischaemic stroke, in an independent cohort of Greek patients and control individuals with no clinical manifestations of vascular disease. Significantly different distributions were observed with respect to the AC008818-1 alleles, with allele 148 associating with an increased risk of stroke incidence, and allele 144 with a protective effect. In addition, the haplotype defined by allele 148 and G allele of SNP45 was found to be significantly increased in patients even though no statistically significant differences emerged with respect to SNP45 alone. The previously established association of a PDE4D gene haplotype with ischaemic stroke in a population from Iceland was independently confirmed in our Greek population, suggesting that PDE4D may be involved in the aetiology and pathogenesis of stroke.

Familial dementia with swollen achromatic neurons and corticobasal inclusion bodies: a clinical and pathological study.

Clinical, pathological and molecular genetic data are presented in two families in which 15 individuals have developed a progressive dementia. Clinical details are available in 10 individuals, neuropathological data in 2. Affected individuals presented between the ages of 43 and 59 years with personality change or memory loss. All individuals developed a progressive dementia with features of frontal lobe dysfunction. Affected individuals commonly developed additional features which included dysphasia, parkinsonism, limb clumsiness and disequilibrium. Duration to death was between 3 and 13 years. Pathological examination of one individual from each family revealed a combination of features not previously described in a familial dementia. Macroscopic examination revealed lobar atrophy. Microscopy revealed neuronal loss and gliosis with swollen achromatic neurons in the cortex and corticobasal inclusion bodies in the substantia nigra. On clinical assessment these families have many features of Pick's disease but pathological examination reveals features more suggestive of corticobasal degeneration.

Exclusion mapping in familial non-specific dementia.

We present genetic linkage data in a large family in which non-specific dementia is inherited as an autosomal dominant trait. We have analyzed 45 highly polymorphic microsatellite sequences and excluded a quarter of the genome as the site of the pathogenic mutation in this family.

A novel silent variant at codon 711 and a variant at codon 708 of the APP sequence detected in Spanish Alzheimer and control cases.

Pathogenic mutations have been identified in exons 16 and 17 of the beta-amyloid precursor protein (APP) gene in some cases of early onset Alzheimer's disease. Screening of these exons in a number of familial and sporadic cases of Alzheimer's disease in Spain, resulted in the identification of a novel silent variant at codon 711 whose relevance to the AD pathogenesis remains unclear. The 708 variant was also detected in one of normal controls.

A locus for familial early-onset Alzheimer's disease on the long arm of chromosome 14, proximal to the alpha 1-antichymotrypsin gene.

Although mutations in the beta-amyloid precursor protein gene (APP) on chromosome 21 cause some cases of early-onset Alzheimer's disease (AD), most cases evidently do not have mutations in APP. We analysed ten early-onset families for linkage to APP and markers elsewhere in the genome. One family (F172) was consistent with linkage to chromosome 21 and was subsequently found to have an APP Val to Ile mutation. Of the others, all but one were consistent with linkage to markers in the middle long arm of chromosome 14. However, no family showed independent evidence of linkage with two point analysis and only one showed independent evidence of linkage on multipoint analysis. Therefore, we cannot rule out heterogeneity at these loci although tests for heterogeneity were not significant.

Screening for mutations in the open reading frame and promoter of the beta-amyloid precursor protein gene in familial Alzheimer's disease: identification of a further family with APP717 Val-->Ile.

Following the identification of mutations in the beta-amyloid precursor protein (APP) gene in familial, early onset Alzheimer's disease (AD), we have developed a screening protocol using single strand conformation analysis (SSCA) to screen exon 17 for the known mutations within APP. In addition, we used this protocol to screen the other seventeen exons of APP and a three hundred and thirty base pair regulatory region of the promoter for new mutations in 9 families with early onset AD. Exons 16 and 17, which encode the deposited beta-amyloid peptide, were screened in a further 10 families. Our screening procedure identifies all the reported mutations within APP. While we have identified a further family with APP717 Val-->Ile, we did not find any previously undescribed mutations. Screening of other exons of APP in 2 families in which we have previously reported mutations at APP717, failed to reveal other sequence abnormalities supporting the hypothesis that the mutations at APP717 cause the disease in these families. These data suggest that mutations in APP are a rare cause of familial early onset AD (3/21 families tested) and that within APP most, possibly all, mutations which cause AD are in exon 17.