Marked diversity of IL23R gene haplotype variants in rheumatoid arthritis comparing with Crohn's disease and ankylosing spondylitis.

Haplotype tagging SNPs of interleukin-23 receptor gene rs1004819, rs7517847, rs7530511, rs2201841, rs1343151 and rs10889677 were determined in 396 patients with rheumatoid arthritis, 190 patients with Crohn's disease, 206 patients with ankylosing spondylitis and 182 controls. Using regression analysis models the rs1004819, rs2201841, and rs10889677 SNPs were found to confer risk for Crohn's disease and ankylosing spondylitis, while rs1343151 had a protective effect in both of these diseases, and the rs2201841 and rs10889677 SNPs showed susceptibility nature for rheumatoid arthritis. Using these SNPs we could study the susceptibility haplotype profiles in these diseases with special attention to the rheumatoid arthritis, first in the literature. Seven different haplotypes could be differentiated. We found that the SNPs exert their susceptibility character in specific haplotype blocks: thus, for rheumatoid arthritis the rs1343151 SNP was risk factor only in a specific haplotype surrounding; this can explain the controversial results published so far about this variant. More importantly, we observed, that while a specific haplotype can confer risk for rheumatoid arthritis, the same haplotype tended to protect against the development of the other two diseases. The data presented here serve evidence for the need of haplotype analysis instead of just single standing SNP analysis when susceptibility to or protection against a certain disease are interpreted.

Difference of interleukin-23 receptor gene haplotype variants in ulcerative colitis compared to Crohn's disease and psoriasis.

OBJECTIVE: Polymorphisms of the interleukin-23 receptor (IL23R) gene have been found to play a role in the development of several autoimmune diseases. Our aim was to examine the possible effect of not only simple individual variants, but of haplotypes composed of them. SUBJECTS: We analysed 263 patients with psoriasis, 199 patients with Crohn's disease (CD), 282 patients with ulcerative colitis (UC), and 253 controls for rs1884444, rs11805303, rs7517847, rs2201841, rs10889677 and rs11209032 variants. METHODS: The genotypes were determined by using PCR/RFLP assay. Logistic regression analysis was used to compare the genotype distribution of the polymorphisms and haplotypes between the examined autoimmune diseases and healthy controls. RESULTS: Rs1884444 was found to confer risk for UC and psoriasis, rs10889677 for CD and psoriasis, while rs2201841 and rs7517847 had effect only in CD. Using these SNPs we could study the susceptibility haplotype profiles in these diseases with special attention to UC. Eight different haplotypes could be differentiated. We found that the SNPs exert their susceptibility character in specific haplotype blocks, and the frequency of one haplotype differed significantly in UC compared with both other diseases and also with healthy controls. This haplotype conferred risk for UC, even while it had a somewhat lower frequency in the other diseases than in controls. CONCLUSIONS: The data presented here serve as evidence for the need of haplotype analysis instead of just single standing SNP analysis when susceptibility is interpreted.

Triglyceride level-influencing functional variants of the ANGPTL3, CILP2, and TRIB1 loci in ischemic stroke.

Stroke is a common multifactorial disease, and the third leading cause of death worldwide, which results in serious long-term mental and physical disability among survivors. The role of affected triglyceride metabolism in the development of ischemic stroke is under extensive investigations. Here, we examined three SNPs, rs12130333 located within the ANGPTL3 locus; rs16996148 residing at the CILP2 gene locus; and rs17321515 at the TRIB1 locus, which were originally reported in association with decreased triglyceride levels; therefore, we investigated their possible protective effect against the development of ischemic stroke. A total of 459 Caucasian stroke patients, stratified as large-vessel, small-vessel, and mixed stroke groups, and 168 control subjects were genotyped using PCR-RFLP methods. As a result, we could not detect any differences in triglyceride or total cholesterol levels in relation to any allelic variants of rs16996148, rs17321515, or rs12130333 SNPs. No correlation was found between the minor alleles rs16996148-T (P = 0.881), rs17321515-G (P = 0.070), or rs12130333-T allele (P = 0.757) and the risk for development of stroke. The data presented here suggest different scale of effect of triglyceride modifier alleles and also their variable susceptibility or protective nature.

Interaction between CTLA4 gene and IBD5 locus in Hungarian Crohn's disease patients.

BACKGROUNDS AND AIMS: The IGR2198a_1 and IGR2096a_1 variants of the IBD5 region were found to be associated with Crohn's disease (CD) in the Hungarian population, while IGR2230a_1 does not seem to confer risk for the disease. In the present study, our aim was to investigate the statistical interaction of these three IBD5 polymorphisms with the +49 A/G substitution within the cytotoxic T lymphocyte antigen-4 (CTLA4) gene, detected previously as neutral gene variant in Hungarian IBD patients. METHODS: A total of 305 unrelated subjects with CD and 310 healthy controls were genotyped with PCR-RFLP methods. RESULTS: In contrast with single gene effects, after genotype stratification, the IGR2198a_1 C and IGR2096a_1 T variants were found to confer susceptibility only in subjects with CTLA4 +49 AA genotype (P = 0.008; OR = 1.86 and P = 0.016; OR = 1.74, respectively), for IGR2230a_1 no such effect on disease risk could be demonstrated. CONCLUSION: Analysis of specific genotype combinations unfolded a possible association between the CTLA4 +49 A/G substitution and two of the observed IBD5 variants with respect to disease risk.

Polymorphisms of the IL23R gene are associated with psoriasis but not with immunoglobulin A nephropathy in a Hungarian population.

Recently, associations were found between autoimmune diseases and variants of interleukin-23 receptor (IL23R) gene; here, we analyzed the association of nine IL23R polymorphisms with psoriasis and with immunoglobulin A nephropathy (IgAN). Groups of patients with psoriasis, IgAN, and controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. We observed a significant increase in the carriage of the minor allele of rs11805303 in psoriasis patients compared to controls. Similarly, for rs2201841 prevalence of the CC genotype and for rs10889677, the AA genotype showed a more than two- and threefold increase, respectively in patients compared to controls. There was no difference in the distribution of IL23R variants between controls and IgAN patients. We confirmed the association of IL23R with psoriasis in a Hungarian population and demonstrated the effect of the rs11805303 SNP, which was tested so far only for other autoimmune diseases. We could not detect any association between the IL23R variants and IgAN.

Genetic variability and haplotype profile of MDR1 (ABCB1) in Roma and Hungarian population samples with a review of the literature.

The genetic variability, haplotype profile and ethnic differences of MDR1 polymorphisms in healthy Roma and Hungarian populations were analyzed and the results were compared with those of other populations available from the literature. Healthy subjects (465 Roma and 503 Hungarian) were genotyped for C1236T, G2677T/A and C3435T variants of MDR1 by PCR-RFLP assay. Differences were found between the Roma and Hungarian populations in the frequencies of MDR1 1236 CC (20.7 vs. 33.2%) and TT genotypes (30.8 vs. 21.9%), in T allele frequency (0.551 vs. 0.443) (p < 0.002), and in 3435T allele frequency (0.482 vs. 0.527, p < 0.04). Furthermore, the frequency of CGC, CGT and CTT haplotypes was significantly higher in the Hungarian population than in Roma (41.4 vs. 35.3%, 9.04 vs. 6.02% and 2.88 vs. 1.08%, respectively; p < 0.009), whereas the frequency of TGC and TTC haplotypes was higher in the Roma population than in the Hungarian (7.31 vs. 1.68% and 6.67 vs. 2.08%, respectively; p < 0.001). The prevalence of MDR1 polymorphisms in the Hungarian population is similar to that of other European populations; however, some differences were observed in the haplotype structures. In contrast, the Roma population differs from Hungarians, from Caucasians and from populations from India in the incidence of MDR1 common variants and haplotypes.

Spinocerebellar ataxia type 2 (SCA2): identification of early brain degeneration in one monozygous twin in the initial disease stage.

Spinocerebellar ataxia type 2 (SCA2) is a progressive autosomal dominantly inherited cerebellar ataxia and is assigned to the CAG repeat or polyglutamine diseases. Recent morphological studies characterized the pathoanatomical features in heterozygous SCA2 patients and revealed severe neuronal loss in a large variety of cerebellar and extra-cerebellar brain sites. In the present study, we examined the brain pathoanatomy of a monozygous twin of a large Hungarian SCA2 family with pathologically extended CAG repeats in both SCA2 alleles. This unique patient was in the initial clinical stage of SCA2 and died almost 3 years after SCA2 onset. Upon pathoanatomical investigation, we observed loss of giant Betz pyramidal cells in the primary motor cortex, degeneration of sensory thalamic nuclei, the Purkinje cell layer, and deep cerebellar nuclei, as well as select brainstem nuclei (i.e., substantia nigra, oculomotor nucleus, reticulotegmental nucleus of the pons, facial, lateral vestibular, and raphe interpositus nuclei, inferior olive). All of these degenerated brain gray matter structures are known as consistent targets of the underlying pathological process in heterozygous SCA2 patients. Since they were already involved in our patient within 3 years after disease onset, we think that we were for the first time able to identify the early brain targets of the pathological process of SCA2.

GCKR gene functional variants in type 2 diabetes and metabolic syndrome: do the rare variants associate with increased carotid intima-media thickness?

BACKGROUND: Recent studies revealed that glucokinase regulatory protein (GCKR) variants (rs780094 and rs1260326) are associated with serum triglycerides and plasma glucose levels. Here we analyzed primarily the association of these two variants with the lipid profile and plasma glucose levels in Hungarian subjects with type 2 diabetes mellitus and metabolic syndrome; and also correlated the genotypes with the carotid intima-media thickness records. METHODS: A total of 321 type 2 diabetic patients, 455 metabolic syndrome patients, and 172 healthy controls were genotyped by PCR-RFLP. RESULTS: Both GCKR variants were found to associate with serum triglycerides and with fasting plasma glucose. However, significant association with the development of type 2 diabetes mellitus and metabolic syndrome could not be observed. Analyzing the records of the patients, a positive association of prevalence the GCKR homozygous functional variants and carotid intima-media thickness was found in the metabolic syndrome patients. CONCLUSIONS: Our results support that rs780094 and rs1260326 functional variants of the GCKR gene are inversely associated with serum triglycerides and fasting plasma glucose levels, as it was already reported for diabetic and metabolic syndrome patients in some other populations. Besides this positive replication, as a novel feature, our preliminary findings also suggest a cardiovascular risk role of the GCKR minor allele carriage based on the carotid intima-media thickness association.

Interaction of the major inflammatory bowel disease susceptibility alleles in Crohn's disease patients.

AIM: To investigate the interaction of interleukin-23 receptor (IL23R) (rs1004819 and rs2201841), autophagy-related 16-like 1 (ATG16L1) (rs2241880), caspase recruitment domain-containing protein 15 (CARD15) genes, and IBD5 locus in Crohn's disease (CD) patients. METHODS: A total of 315 unrelated subjects with CD and 314 healthy controls were genotyped. Interactions and specific genotype combinations of a total of eight variants were tested. The variants of IBD5 locus (IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868), CARD15 (R702W rs2066845 and L1007fs rs2066847), ATG16L1 (rs2241880) and IL23R (rs1004819, rs2201841) genes were genotyped by PCR-RFLP, the G908R (rs2066844) in CARD15 was determined by direct sequencing. RESULTS: The association of ATG16L1 T300A with CD was confirmed [P = 0.004, odds ratio (OR) = 1.69, 95% CI: 1.19-2.41], and both IL23R variants were found to represent significant risk for the disease (P = 0.008, OR = 2.05, 95% CI: 1.20-3.50 for rs1004819 AA; P < 0.001, OR = 2.97, 95% CI: 1.65-5.33 for rs2201841 CC). Logistic regression analysis of pairwise interaction of the inflammatory bowel disease (IBD) loci indicated that IL23R, ATG16L1, CARD15 and IBD5 (IGR2198a_1) contribute independently to disease risk. We also analysed the specific combinations by pair of individual ATG16L1, IL23R rs1004819, rs2201841, IGR2198a_1, IGR2096a_1 and CARD15 genotypes for disease risk influence. In almost all cases, the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one polymorphism. The highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status (P < 0.001, OR = 9.15, 95% CI: 2.05-40.74). CONCLUSION: The present study suggests a cumulative effect of individual IBD susceptibility loci.

Functional variants of glucokinase regulatory protein and apolipoprotein A5 genes in ischemic stroke.

Both the natural variants of the apolipoprotein A5 (APOA5) and the glucokinase regulatory protein gene (GCKR) have been shown to associate with increased fasting triglyceride levels. Here, we investigated the possible association of the functional variants of these two genes with non-fasting triglyceride levels and their susceptibility nature in ischemic stroke. A total of 513 stroke patients and 172 healthy controls were genotyped. All the APOA5 variants (T-1131C, IVS3 + G476A, C56G, and T1259C) were associated with increased triglyceride levels in all stroke patients and controls; except for T1259C, they all conferred risk for the disease. No such association was found for the examined GCKR rs1260326 (C1337T) variant. Furthermore, we examined the effects of specific combinations of the GCKR rs1260326 and APOA5 polymorphisms. Our findings confirmed the previous results regarding the association of APOA5 variants with triglyceride-level increase and stroke susceptibility of these alleles. By contrast, we could not detect any association of the studied GCKR allele with triglyceride levels or with the susceptibility of stroke in the same cohort of patients. In addition, the effect of APOA5 did not change significantly when specific combinations of the two genes were present.

Association of ARTS1 gene polymorphisms with ankylosing spondylitis in the Hungarian population: the rs27044 variant is associated with HLA-B*2705 subtype in Hungarian patients with ankylosing spondylitis.

OBJECTIVE: Associations have been found between ankylosing spondylitis (AS) and polymorphisms in the aminopeptidase regulator of TNFR1 shedding (ARTS1) gene. We studied the association of 5 polymorphisms within the ARTS1 gene with AS in Hungarian patients. We also investigated the prevalence of HLA-B27 subtypes in the Hungarian population. METHODS: A case-control study including 297 patients with AS and 200 sex and ethnically matched healthy controls was performed. Patients and controls were genotyped for rs27044, rs17482078, rs10050860, rs30187, and rs2287987 single-nucleotide polymorphisms using real-time polymerase chain reaction (PCR) allelic discrimination. HLA-B27 subtypes were determined with PCR sequence-specific primer (PCR-SSP) technique. RESULTS: We observed a significant increase in the minor allele frequency of rs27044 (p = 0.001) in the AS group compared to controls. The minor allele frequencies of rs10050860 (p = 0.006) and rs2287987 (p = 0.002) showed a significant decrease in AS patients compared to controls. Haplotype analysis revealed association of 2 ARTS1 haplotypes with AS in the Hungarian population. We found that HLA-B*2705 was the predominant subtype in Hungarians with AS. Carriage of the G allele of rs27044 was significantly associated with the HLA-B*2705 subtype (p = 0.009) in AS patients. CONCLUSION: We confirmed reported associations of ARTS1 gene polymorphisms with AS in a Hungarian cohort study. We found HLA-B*2705 as the predominant subtype in Hungarian AS patients in accord with other studies on Caucasian populations. Our results suggest that the ARTS1 gene variants together with HLA-B27 strongly contribute to disease susceptibility in patients with AS.

Interleukin-23 receptor gene variants in Hungarian systemic lupus erythematosus patients.

OBJECTIVE: We investigated the association between systemic lupus erythematosus (SLE) and polymorphisms of interleukin-23 receptor (IL23R) gene, which was recently found to be associated with autoimmune diseases, including Crohn's disease, rheumatoid arthritis, psoriasis and ankylosing spondylitis. SUBJECTS: We analysed 383 SLE patients and 253 controls for rs11805303, rs10889677, rs1004819, rs2201841, rs11209032, 11209026, rs10489629, rs7517847 and rs7530511 variants. METHODS: The analysis was carried out using PCR-RFLP methods. Logistic regression analysis was used to compare the genotype distributions of the polymorphisms and haplotypes between the SLE patients and healthy controls. RESULTS: We observed no significant difference of the examined variants between the patient and control groups. CONCLUSIONS: Our results suggest that neither single nucleotide variants nor haplotypes of IL23R indicate susceptibility to developing SLE in the Hungarian population.

[Possible role of selected IGR and SLC22A4/SLC22A5 loci in development of inflammatory bowel diseases]. / Az 5q31 IBD5-régióban található IGR és SLC22A4/SLC22A5 variánsok lehetséges szerepe a gyulladásos bélbetegség kialakulásában.

UNLABELLED: The IBD5 locus (MIM#606348) on chromosome 5q31 has been demonstrated to confer increased risk for inflammatory bowel disease. Controversial reports have been published about the significance of individual loci located in this region. Here we investigated the possible genetic association of inflammatory bowel diseases with C1672T of SLC22A4 and G-207C SLC22A5 alleles, and with IGR2096a_1 (rs12521868) and IGR2198a_1 (rs11739135) susceptibility variants of the IBD5 region located on chromosome 5q31. PATIENTS AND METHODS: Total of 440 patients, 206 with Crohn's disease, 234 with ulcerative colitis, and 279 controls were studied by PCR-RFLP methods. RESULTS: Neither the C1672T, and G-207C alleles, nor the TC haplotype were found to confer risk for Crohn's disease or ulcerative colitis. By contrast, both of the minor allele frequencies of IGR2096a_1 T (48.1%) and IGR2198a_1 C (46.1%) were increased in Crohn's disease subjects as compared with the controls (38.5% and 38.4%, respectively; p<0.05). Using regression analysis adjusted to age and gender these alleles were found to confer risk for Crohn's disease (OR=1.694, 95% CI: 1.137-2.522; p=0.010 for T allele, OR=1.644, 95% CI=1.103-2.449; p=0.015 for C allele of IGRs). In UC no such associations were found. CONCLUSIONS: Our results revealed the susceptibility nature of the examined IGR minor alleles in Hungarians, which nation differs historically from the surrounding Caucasian populations in origin of the founders of the state.

Vitamin K epoxide reductase complex 1 (VKORC1) haplotypes in healthy Hungarian and Roma population samples.

The aim of this work was to determine the VKORC1 haplotype profile in healthy Hungarian and Roma population samples, and to compare our data with other selected populations. Using haplotype tagging SNPs (G-1639A, G9041A and C6009T), we characterized Hungarian (n = 510) and Roma (n = 451) population samples with regard to VKORC1*1, *2, *3 and *4 haplotypes. In the Hungarian samples, the VKORC1*1, *2, *3 and *4 haplotypes accounted for 3, 39, 37 and 21%, respectively and by contrast, in the Roma population samples the VKORC1 variants were 5, 30, 46 and 19%, respectively. Comparing the genotypes of Roma and Hungarian populations, difference was found in the *2/*2 (6.87 vs 13.5%), *2/*4 (13.9 vs 19.2%) and *3*3 (21.9 vs 13.7%) VKORC1 haplotype combinations. Comparing each group with the others, and our data with findings published previously by other groups, the VKORC1 genetic profile in Hungarians was more similar to European Caucasians and Americans with European descent than to Roma samples. Clear differences could be detected between Roma versus Hungarians and European or American Caucasians; the Roma population had only minor similarities with data from India.

IGR2096a_1 T and IGR2198a_1 C alleles on IBD5 locus of chromosome 5q31 region confer risk for Crohn's disease in Hungarian patients.

BACKGROUND AND AIMS: We investigated the possible association of IBD with C1672T of SLC22A4 and G-207C of SLC22A5 alleles, and with the novel IGR2096a_1 (rs12521868) and IGR2198a_1 (rs11739135) susceptibility loci, all located on IBD5 locus of chromosome 5q31. MATERIALS AND METHODS: DNA of 217 Crohn's disease, 252 ulcerative colitis, and 290 control patients were analyzed by polymerase chain reaction/restriction fragment length polymorphism methods. RESULTS: Neither the C1672T and G-207C alleles, nor the TC haplotype were found to be risk factors. By contrast, the minor allele frequencies of IGR2096a_1 T (47.2%) and IGR2198a_1 C (45.9%) were increased in Crohn's disease compared with the controls (38.2% and 37.7%, respectively; p < 0.05); multivariate regression analysis revealed a risk nature for Crohn's disease (OR = 1.748, 95% CI 1.186-2.574; p = 0.007 for T allele, OR = 1.646, 95% CI 1.119-2.423, p = 0.011 for C allele of IGRs). CONCLUSION: The data suggest a special haplotype arrangement of susceptibility genes at the IBD5 locus in Hungarians, which nation differs historically from the surrounding Caucasian ethnicities in its origin.

Apolipoprotein A5 gene IVS3+G476A allelic variant confers susceptibility for development of ischemic stroke.

BACKGROUND: T-1131C, T1259C and IVS3+G476A are naturally occurring variants of the apolipoprotein A5 (APOA5) gene and their possible impact on the development of ischemic stroke was investigated in the present study. METHODS AND RESULTS: PCR-RFLP assays were used to determine the distributions of the APOA5 alleles in small-vessel, large-vessel and mixed subgroups of 378 patients and in 131 stroke-free control subjects. Increased triglyceride levels were found in subjects carrying -1131C, 1259C, IVS3+476A alleles in all stroke groups and in the controls. The -1131C and IVS3+476A alleles, but not the T1259C variant, showed significant accumulation in all stroke subgroups. Logistic regression analysis adjusted for age, gender, body mass index, total cholesterol level, ischemic heart disease, hypertension, diabetes mellitus, smoking-and drinking habits revealed that the IVS3+476A allele represents independent susceptibility factor for stroke (odds ratio for small-vessel: 4.748; large-vessel: 3.905; mixed: 2.926; overall: 3.644 at 95% confidence interval; p<0.05), we could also confirm the previously verified pathogenic role of the -1131C variant. CONCLUSIONS: All of the 3 APOA5 variants are associated with elevated triglycerides, but only the -1131C and the IVS3+476A alleles confer risk for all types of ischemic stroke; such an association could not be detected for the 1259C allele.

[Pseudo-Bartter syndrome in a case of cystic fibrosis caused by C1529G and G3978A compound heterozygosity]. / Pszeudo-Bartter-szindróma kialakulása kapcsán felismert C1529G- és G3978A-mutációk együttese által okozott cisztás fibrosis.

The 8-month-old patient was hospitalized after a few days of apathy and feeding difficulty with moderate exsiccation. Severe hypokalemia, hyponatremia, hypochloremia associated with alkalosis were found, which were accompanied by the decreased urinary electrolytes and elevated serum renin and aldosterone, therefore the condition corresponded to a pseudo-Bartter syndrome. The diagnosis of cystic fibrosis was arisen, which was established by the elevated sweat chloride levels. Sequencing of the 27 exons of the cystic transmembrane regulator gene two rare mutations were detected in compound heterozygous form: in the exon 10 a C1529G transversion, whereas in the exon 20 a G3978A transition was verified, both of them result in development of premature stopcodons (S466X and W1282X, respectively). Carriage of first mutation could be found in the asymptomatic mother, while the other one was identified in the father. In the proband and in the mother a G3341A mutation was also detected in exon 17, which causes an R1070Q amino acid change. However, this likely cannot associate with pathology since the existing premature stopcodon on the same allele does not allow synthesis of protein. These mutations have been described in combination with delta F508 mutation, however, their simultaneous presence in the same subject has not been reported. During the one and half year follow-up the clinical picture appeared benign.

3'UTR C2370A allele of the IL-23 receptor gene is associated with relapsing-remitting multiple sclerosis.

The interleukin (IL) -23/IL-17 cytokine axis has been suggested to play an important role in the development of several autoimmune diseases including multiple sclerosis. Here, we compared the prevalence of C2370A single nucleotide polymorphism (SNP) in the 3' untranslated region (3'UTR) of the IL-23 receptor (IL23R) between 223 patients with relapsing-remitting multiple sclerosis (RRMS) and 200 healthy controls. The A2370A genotype was significantly over-represented among patients with RRMS (10.8%) and RRMS exhibiting oligoclonal bands in the cerebrospinal fluid (12.9%) when compared to healthy subjects (5.50%). Multiple regression analysis revealed that presence of AA genotype provides a two-fold risk for the development of multiple sclerosis (OR=2.072, 95% CI: 0.988-4.347, p<0.05). These data indicate that IL23R represents a novel shared susceptibility gene as its association with inflammatory bowel disease (IBD) has recently been verified.

[The autosomal dominant cerebellar ataxias are hereditary neurodegenerative diseases]. / Autoszomális domináns öröklodésu cerebellaris ataxiák.

Even before a few decades ataxias were among the least understood neurological disorders but the clarification of their molecular background provides possibility for the accurate establishment of the diagnosis and gives a hand in the explanation of numerous extraordinary phenomena, like variable phenotypes in the same family. The cognition of the pathogenesis of spinocerebellar ataxias can grant a chance to the development of successful therapies instead of the present available merely symptomatic treatments. The rapid discovery of many genes and loci together with the segregation of ataxia subtypes can, however, cause inconvenience in the precise determination of the disorder. Our aim was to provide insight to the genetic background of these neurodegenerative diseases and also to give help in the correct diagnosis by the short description of the major ataxia subtypes.

Apolipoprotein A5 T-1131C variant confers risk for metabolic syndrome.

The -1131C is a naturally occurring variant of the apolipoprotein A5 (ApoA5) gene, which has been shown to associate with increased triglyceride levels. This variant has also been shown to confer risk for development of ischemic heart disease and stroke. The gene is in linkage disequilibrium with factors known to correlate with impaired glucose homeostasis. These observations prompted us to study the prevalence of the ApoA5 -1131C allele in patients with metabolic syndrome. A total of 201 metabolic syndrome patients and 210 controls were studied. In both groups the triglyceride levels of patients with -1131C allele were significantly increased compared to the subjects with -1131T allele (3.22+/-0.43 mmol/l vs. 2.24+/-0.12 mmol/l, p<0.01 in the metabolic syndrome patients; 2.10+/-0.19 mmol/l vs. 1.22+/-0.05 mmol/l, p<0.01 in the controls). In metabolic syndrome patients the prevalence of the ApoA5 -1131C variant was increased compared to the healthy controls (11% vs. 6.20%). Multiplex regression analysis model adjusted for age, gender, serum total cholesterol levels, acute myocardial infarction and stroke events revealed that the examined ApoA5 variant confers risk for the development of metabolic syndrome: the odds ratio at 95% confidence interval was 3.622 (1.200-10.936), p=0.02. Our findings strongly suggest that this variant is a risk factor for the development of hypertriglyceridemia and metabolic syndrome.