Novel Olig 1-coding variants and susceptibility to multiple sclerosis.
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Adult↗
Biomedical subjects
A Goris
Publications and source records attributed to A Goris.
No evidence for association with Parkinson disease for 13 single-nucleotide polymorphisms identified by whole-genome association screening.
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Adult↗
Prevalence of the LRRK2 G2019S mutation in a UK community based idiopathic Parkinson's disease cohort.
The LRRK2 G2019S mutation is the commonest genetic cause of Parkinson's disease (PD) identified to date, although estimates of its prevalence in idiopathic disease vary considerably. Our objectives were to determine G2019S mutation frequency in an unselected, community based cohort of idiopathic PD cases from the UK and to describe phenotypic characteristics among carriers. The mutation was present in two of 519 cases (0.4%) and none of 887 control individuals. The true prevalence of the mutation in idiopathic disease, its penetrance, and the phenotypic heterogeneity of associated cases have important implications for genetic screening in the clinical field.
Adult↗
The CTLA4 +49 A/G*G-CT60*G haplotype is associated with susceptibility to multiple sclerosis in Flanders.
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system white matter characterized by inflammation, demyelination and axonal damage. The cytotoxic T lymphocyte antigen-4 (CTLA-4) protein plays a key role in the down-regulation of T cell activation. We analysed the CTLA4 +49A/G and CT60 polymorphisms in a cohort of 120 MS trio families recruited from the Flanders region in Belgium. Both polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (RFLP). The +49 G-allele was significantly more transmitted to affected probands (P = 0.005). No transmission distortion was observed for the CT60 polymorphism. Haplotype analysis revealed significant overtransmission of the +49 A/G*G-CT60*G haplotype (P = 0.0025), and undertransmission of the +49 A/G*A-CT60*G haplotype (P = 0.015). The CTLA4 gene has been the focus of intense investigation in MS. Of 15 recently published papers, only six reported significant associations of various CTLA4 polymorphisms with MS, with the remainder being negative. Ours is the first report investigating the CT60 polymorphism in MS. Our data highlight a need for further scrutiny of the CTLA4 gene in MS.
Adult↗
IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis.
Interferon-gamma (IFNgamma) treatment is deleterious in multiple sclerosis (MS). MS occurs twice as frequently in women as in men. IFNgamma expression varies by gender. We studied a population-based sample of US MS patients and ethnicity-matched controls and independent Northern Irish and Belgian hospital-based patients and controls for association with MS, stratified by gender, of an intron 1 microsatellite [I1(761)*CAn], a single nucleotide polymorphism 3' of IFNG [3'(325)*G --> A] and three flanking microsatellite markers spanning a 118 kb region around IFNG. Men carriers of the 3'(325)*A allele have increased susceptibility to MS compared to noncarriers in the USA (P=0.044; OR: 2.58, 95% CI: 0.97-8.08) and Northern Ireland (P=0.019; OR: 2.37, 95% CI: 1.10-5.13). There is a nonsignificant trend in the same direction in Belgian men (P=0.299; OR: 1.50, 95% CI: 0.71-3.26). Men carriers of I1(761)*CA13, which is in strong linkage disequilibrium with the 3'(325)*A, have increased susceptibility (P=0.050; OR: 2.22, 95% CI: 0.98-5.40), while men carriers of I1(761)*CA12 have decreased susceptibility (P=0.022; OR: 0.46, 95% CI: 0.23-0.90) to MS in the USA. Similar associations were reported in Sardinia between the I1(761)*CA12 allele and reduced risk of MS in men. Flanking markers were not associated with MS susceptibility. Polymorphisms of IFNG may contribute to differences in susceptibility to MS between men and women.
3' Flanking Region↗
Polymorphisms in the interleukin-4 and IL-4 receptor genes and multiple sclerosis: a study in Spanish-Basque, Northern Irish and Belgian populations.
Cytokine gene polymorphisms are known to influence susceptibility and disease course of many autoimmune diseases. Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system white matter characterized by inflammation, demyelination and axonal damage. We analysed both the well-known intronic variable number of tandem repeat (VNTR) and +33 C/T single-nucleotide polymorphisms (SNP) in the IL-4 gene, as well as the functional Q551R SNP in the IL4-R gene in a cohort of three distinct populations comprising sporadic cases and controls from the northern Spanish Basque Country and Northern Ireland, as well as family trios from Belgium. The IL-4 +33 TT genotype was decreased in primary progressive (PP) versus relapsing-remitting (RR) patients in the Northern Irish population (OR = 0.14; 95% CI = 0.018-1.09). Two-marker haplotype distribution of the VNTR and +33 C/T SNP in PP patients differed from that seen in RR patients in Northern Ireland (P = 0.03). The R allele of the Q551R SNP was significantly under-transmitted in the Belgian trio families (P = 0.003), although this effect was not seen in the Northern Irish and Basque data sets. We did not identify IL-4-IL4-R gene-gene interaction in determining susceptibility or clinical parameters of MS. Disease or genetic heterogeneity or both may be responsible for the observed lack of reproduction in different populations. Our data reinforce recent findings for a role of IL4-R in susceptibility to MS.
Adult↗
Polymorphisms in the interferon-gamma/interleukin-26 gene region contribute to sex bias in susceptibility to rheumatoid arthritis.
OBJECTIVE: To determine whether polymorphisms in the interferon-gamma (IFNgamma)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA). METHODS: Four microsatellite markers, located in a 118-kb interval that contains both the IFNgamma and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction-based fragment analysis. RESULTS: Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [P(corr)] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002, P(corr) = 0.03) but not in men with RA. CONCLUSION: Our results demonstrate that common polymorphisms in the IFNgamma/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis.
Adult↗
Gelatinase B, PECAM-1 and MCP-3 gene polymorphisms in Belgian multiple sclerosis.
Polymorphic microsatellite markers in the genes for gelatinase B, PECAM-1 and MCP-3 have previously been analysed in Swedish and Sardinian individuals to test for association with multiple sclerosis (MS). Confirmation and comparison of genetic associations in various ethnic populations is mandatory and, therefore, we studied these three gene polymorphisms in 216 clinically definite MS patients and 193 normal controls, and in 148 simplex MS families, all of Belgian origin. No allelic associations were found between MS and the CA microsatellite marker in the promoter region of the gelatinase B gene, and the polymorphic CA repeat in the sixth intron of PECAM1. However, the two most abundant alleles of the CA/GA microsatellite polymorphism in the promoter-enhancer region of the MCP-3 gene, A2 (109 bp) and A3 (111 bp), were found to be significantly associated with disease in the case-control study [OR (95% CI)=0.68 (0.51-0.92), p (1 df)=0.015 and OR (95% CI)=1.62 (1.22-2.14), p (1 df)=0.0010, respectively], but not in the family study. These results are in agreement with previous findings in the Swedish and Sardinian populations and reinforce the possibility of a role for chemokines in MS pathogenesis.
Adult↗
Linkage disequilibrium analysis of chromosome 12q14-15 in multiple sclerosis: delineation of a 118-kb interval around interferon-gamma (IFNG) that is involved in male versus female differential susceptibility.
We have recently reported the association of a polymorphic intronic CA-repeat in the interferon-gamma gene (IFNG) with gender bias in susceptibility to multiple sclerosis (MS) in a Sardinian population. This association could refer to a functional polymorphism within IFNG or could be due to linkage disequilibrium between the IFNG marker and a neighbouring susceptibility locus. Within the average reach of linkage disequilibrium, various other candidate genes are located. Among these the most striking ones are the genes coding for the cytokines interleukin-22 (IL-22) and interleukin-26 (IL-26) that constitute together with IFNG a cytokine cluster on chromosome 12q14. To determine more precisely the location of this gender-associated susceptibility locus, we have now performed a more extensive linkage disequilibrium screen of this region using nine additional microsatellite markers. This locus appeared to be confined to a 118-kb interval that is bordered by the markers D12S313 and D12S2511, in which IFNG itself remains the main candidate gene. Haplotype analysis confirmed that this MS-associated locus protects males from developing MS according to a recessive or allele-dosage model. Our results indicate that the well-documented gender differences in susceptibility to MS are at least partially caused by genetic factors in the region surrounding IFNG.
Adolescent↗
Novel polymorphisms in the IL-10 related AK155 gene (chromosome 12q15).
AK155 is a recently discovered cytokine distantly related to IL-10. Its gene is located on chromosome 12q15, a region that is likely to harbour susceptibility genes for autoimmune and allergic diseases. We provide here identification and characterization of two microsatellite polymorphisms at the AK155 locus, i.e. D12S2511 and D12S2510. The first is located in the third intron and the second in the 3' region of the gene. Both might be useful as markers in association or linkage studies of polygenic inflammatory or allergic diseases. No association with multiple sclerosis was found for each of these markers by means of the transmission disequilibrium test in an extended number of Sardinian simplex families.
Alleles↗
High-resolution analysis of IL-6 minisatellite polymorphism in Sardinian multiple sclerosis: effect on course and onset of disease.
A minisatellite polymorphism located in the 3' flanking region of the interleukin-6 (IL-6) gene was analysed in 192 Sardinian simplex families with multiple sclerosis (MS). By applying a high-resolution sizing approach, 9 alleles were identified. None of these were associated with in globo susceptibility to MS as shown by transmission disequilibrium testing. Analysis of clinically different groups showed that the A5 allele was associated with a benign (P = 0.007) but not with a malignant (P = 0.45) course of disease. In particular, the frequency of the A5/A5 genotype was significantly higher in patients with benign MS (P = 0.002). In addition, carriage of any of the larger alleles (A6-->A9) was associated with accelerated onset of disease (P = 0.025). Our results suggest that allelic variations in the IL-6 gene may predispose to alterations in the course and initial onset of MS.
Adult↗
Tissue depletion and health related quality of life in patients with chronic obstructive pulmonary disease.
The relationship between tissue depletion and decreased exercise performance has been well established in patients with COPD. In this study we investigated the influence of the pattern of tissue depletion on health related quality of life (HRQL) and their mutual relationship with exercise capacity and dyspnoea. Patients with low body weight and/or low fat-free mass (FFM; using bioelectrical impedance) were categorized in three groups according to type of tissue depletion: loss of both FFM and fat mass (FM), and loss of FFM or FM only. Handgrip strength (HGS) was used as a functional outcome measure of tissue depletion. Exercise performance was assessed by 12 min walking distance (12MWD) and dyspnoea by visual analogue scale (VAS). HRQL was measured with the St George's Respiratory Questionnaire (SGRQ) and the Medical Psychological Questionnaire for Lung diseases (MPQL). Patients with depletion of FFM irrespective of body weight showed greater impairment in 12MWD, HGS, the 'activity' and 'impact' scores of the SGRQ and the domain 'invalidity' of the MPQL, in comparison with depleted patients with relative preservation of FFM. Exercise performance and dyspnoea were also significantly related to these subscores of HRQL. In addition, dyspnoea related significantly to the domain 'symptoms' of the SGRQ. Tissue depletion pattern remained significantly related to SGRQ-scores and the domain 'invalidity' of the MPQL when dyspnoea and walking distance were added to the model as a covariates. Tissue depletion is an important determinant of HRQL independent of exercise capacity and dyspnoea.
Aged↗
Maxillary distraction osteogenesis: a method with skeletal anchorage.
Maxillary distraction osteogenesis is a challenging technique to treat severe maxillary retrusion. Maxillary advancement by distraction has the advantage to provide new bone in combination with simultaneous expansion of the soft-tissue functional matrix. Cleft lip and palate patients can present with severe maxillary retrusion and Class III malocclusion. Two 13-year-old patients, born with non-syndromic cleft lip and palate, underwent maxillary distraction--one had a bilateral, the other a unilateral complete cleft lip and palate. Maxillary advancement was performed using an external distraction device in combination with titanium miniplates as a skeletal maxillary anchorage. After a complete Lefort I osteotomy with pterygomaxillary disjunction, a latency period of 3 days was respected. On the fourth postoperative day, distraction was initiated at the rate of 1 mm/d. Preoperative clinical photographs, dental casts, lateral cephalograms, and panoramic radiographs were taken. Further lateral cephalograms were obtained after the latency period, after completion of the active period of distraction, at the completion of the consolidation period, and at 6 and 12 months postoperatively. The aesthetic outcome was excellent and skeletal advancement of 8 and 7 mm was measured without dentoalveolar compensations.
Adolescent↗
Analysis of an IFN-gamma gene (IFNG) polymorphism in multiple sclerosis in Europe: effect of population structure on association with disease.
An intronic dinucleotide polymorphism in the IFN-gamma gene (IFNG) was used as a marker for testing association with multiple sclerosis (MS). Disease association was analyzed in case-control sets sampled from four geographically separate European populations (Germany, Northern Italy, Sardinia, and Sweden). Only in the Swedish was a weak disease association of the IFNG allele pattern found, mainly due to a higher frequency of IFNG allele I1 in MS patients. No evidence for association was found in the German or Northern Italian populations. These results contrast with the situation in Sardinia. We have recently reported transmission disequilibrium of IFNG allele I2 in Sardinian MS siblings not carrying the predisposing DRB1 *03 or *04 alleles (Ann. Neurol. 44, 841-842, 1998). Further analysis now shows that I2 is significantly more often transmitted to DRB1 *03-/*04- males, than to DRB1 *03-/*04- females. The odds ratio (OR) for IFNG-associated susceptibility to MS in the total Sardinian DRB1*03-/*04- group was 1.88 for I2 heterozygotes but amounted to 8.235 for I2 homozygotes, suggestive of a recessive mode of inheritance. Score test-based statistics pointed to an I2 allele dosage effect acting in susceptibility. Comparison of the IFNG allele frequencies in seven European populations (Northern Finnish, Southern Finnish, Swedish, Danish, German, Italian, and Sardinian) revealed a highly different distribution pattern. We introduced latitude as a score variable in order to test for trend in binomial proportions. This test statistic showed that for both most common alleles, I1 and I2 (compiled allele frequency about 85%), a significant opposite north-to-south trend is seen throughout Europe. This effect is primarily due to the extreme values found in the outlier populations of Finland and Sardinia. Our findings are discussed with respect to recent literature pertinent to the role of the IFNG chromosome region in autoimmune diseases.
Alleles↗
A dinucleotide repeat polymorphism located in the IFN-alpha/beta gene cluster at chromosome 9p22 is not associated with multiple sclerosis in Sardinia.
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Chromosomes, Human, Pair 9↗
Interferon-gamma gene polymorphism-associated risk for multiple sclerosis in Sardinia.
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Alleles↗
Evaluation of a newly developed HIV antigen test.
A new monoclonal antibody-based enzyme immunoassay (Innogenetics) for the detection and quantification of p24 core antigens of HIV-1 (group M and group O) and of HIV-2 was evaluated on 2745 serum samples and 18 culture supernatants and compared with a reference (Coulter) HIV-1 p24 antigen assay. Positive results were confirmed by neutralization with the reagents of the respective tests. As demonstrated by dilution series of HIV cocultures, the new test recognizes p24 antigen of the most common HIV genetic subtypes, including group O and HIV-2. Titres ranged from 729 to 531441. Therefore p24 antigen assay is but very weakly reactive with HIV-2 (titres from 9 to 81). The new test is considerably more sensitive than the reference. In a population of 365 follow-up samples from 86 different patients, representing all stages of infection, the new test detected p24 antigen at least once in 52% (45/86) of these patients, whereas the reference was positive in 31% (27/86). The newly designed test detected antigen in 40% (145/365) of the samples, while the reference was positive in 21% (75/365). In a group of PCR and/or culture positive neonates, 33% (9/27) of the samples were positive with the new test versus 18% (5/27) with the reference. The specificity of the new test, as determined on 2,000 blood donor samples, was 99.65% (initially), 99.80% (after repetition), and 100% (with neutralization). The reference scored 99.95%, 100%, and 100%, respectively. In 300 seronegative samples from persons at risk, the initial specificity of the new test was 98.67% (the reference, 99.00%). With neutralization, both assays were 100% specific.
Antibodies, Monoclonal↗
Social deprivation and psychiatric admission rates in Amsterdam.
The main subject of this study was the link between social indicators and the (re)admission rates for, and length of stay in, in-patient mental health care in Amsterdam. In a factor analysis of 15 sociodemographic variables, two principal components analysis factors were distinguished: housing quality and socioeconomic deprivation. The census variables and the factors almost all had high correlations with the crude admission rates as well as the rates standardised for age and sex. In general, the correlations with rates that were also standardised for marital status were significantly lower. This shows that many correlations between indicators and crude rates are determined to a significant extent by the marital status profile of an area. Socioeconomic deprivation is positively correlated with the proportion of readmissions and inversely correlated with average length of stay.
Adolescent↗