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BACKGROUND: Roadside trauma in India is an increasingly significant problem, particularly because of bad roads, irregular road signs, overcrowding, overspeeding, and bad traffic etiquettes. Adequate information on the characteristics of victims, causes of accidents, frequency, vehicles involved, alcohol intake, and outcome of management is essential for understanding and planning for better management. AIM: This study aimed to determine the characteristics of trauma (roadside accidents) victims admitted to various trauma centers in India. The purpose of this study is to examine the epidemiology of trauma within a local community in India through data gained from the different emergency centers and to analyze trauma patients to find the predictors that led to the deaths of trauma patients. MATERIALS AND METHODS: The present observational study involved trauma victims over 1-year period in three centers. Demographical details recorded were age, sex, alcohol intake, systolic blood pressure on arrival, respiratory rate, Glasgow Coma Scale (GCS) score, the interval between injury and admission, Injury Severity Score (ISS) risk factors, hospital stay, and outcome. RESULTS: A total of 2650 injuries were recorded in 2466 patients. The mean age was 42.45 ± 15.7 years, the mean ISS was 13.82 ± 6.2, and the mean GCS was 12.20 ± 4.1. The mean time to admission at different trauma centres was 48.41 ± 172.8 h. The head injury was the most common (29.52%). CONCLUSION: Road side accidents due to overspeeding was the most common cause whereas driving under the effect of alcohol was the second most common cause. Accidents are common because of bad traffic etiquette on Indian roads.
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The potential for practical application of fly ash, zinc slag and their blends for geopolymer synthesis at ambient temperature have been investigated in this paper. Fly ash is an alumino-silicate byproduct suitable for geopolymer reaction, but its low reactivity at ambient condition is the restriction of its bulk utilization. Above limitation can be overcome by blending with zinc slag (ZS). Additionally, ZS contains heavy and toxic metals (Pb, Zn, Cr, Cd, As), which can be stabilize in Al-Si based geopolymer network structure. Isothermal conduction calorimetry (ICC) is used to monitor the geopolymer reaction with time. Slag rich specimens are characterized with higher rate of reaction with augmented peak. The mineralogy and microstructure of the geopolymers have been examined through X-ray diffraction and scanning electron microscope. The detected chief reaction product is N-(C)-A-S-H and C-(N)-A-S-H1 type hydrated gel. Continual improvement of compressive strength of the geopolymers with increasing slag content is explained with higher degree of reaction, formation of more reaction products and development of compact microstructure. According to toxicity characteristic leaching procedure (TCLP), toxic metals leaching is within permissible limit. Paver blocks using 40-80â¯wt% ZS has been developed, which meets IS 15,658: 2006 standard and comply with US-EPA specification.
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The variation of amplitude and transit time of the diffracted signal from the crack-tip in complex geometry components and their resulting effect on the probability of detection (POD) and probability of sizing (POS) was studied. The diffracted signal amplitude has been evaluated from the standard expressions for diffraction coefficient, spatial attenuation and the transit time from the respective mathematical models for both vertical and inclined cracks. The same parameters namely the signal amplitude and the transit time have been measured through experiments conducted on simulated test specimens. It has been observed that the analytical and experimental results compare well with each other. Based on this result the trend and shape (width of the transition zone) of the POD/POS curves can be predicted.
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Algoritmos , Artefactos , Materiales Manufacturados/análisis , Ensayo de Materiales/métodos , Modelos Teóricos , Ultrasonografía/métodos , Simulación por ComputadorRESUMEN
Thermal sprayed hydroxyapatite coatings suffer from poor mechanical properties like tensile strength, wear resistance, hardness, toughness and fatigue. The mechanical properties of hydroxyapatite coatings can be enhanced via incorporation of secondary bioinert reinforcement material. In this study an attempt has been made to improve the mechanical properties of plasma sprayed hydroxyapatite by reinforcing it with 10, 20 and 30% Al2O3. The plasma sprayed coatings have been characterized using FE-SEM/EDAX, XRD, AFM and FTIR spectroscopy. Corrosion studies have been done in simulated body fluid and abrasive wear studies have been performed on flat specimens on a disk wear tester. Microhardness, tensile strength and wear resistance are found to be increased with increasing Al2O3 content. All types of coatings show superior resistance against corrosion in simulated body fluid.
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Óxido de Aluminio/química , Materiales Biocompatibles Revestidos , Durapatita/química , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Gases em Plasma , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie , Resistencia a la Tracción , Difracción de Rayos XRESUMEN
Dose escalation with intensity-modulated radiation therapy (IMRT) for carcinoma of the prostate has augmented the need for accurate prostate localization prior to dose delivery. Daily planar kilovoltage (kV) imaging is a low-dose image-guidance technique that is prevalent among radiation oncologists. However, clinical outcomes evaluating the benefit of daily kV imaging are lacking. The purpose of this study was to report our clinical experience, including prostate motion and gastrointestinal (GI) and genitourinary (GU) toxicities, using this modality. A retrospective analysis of 100 patients treated consecutively between December 2005 and March 2008 with definitive external beam IMRT for T1c-T4 disease were included in this analysis. Prescription doses ranged from 74-78 Gy (median, 76) in 2 Gy fractions and were delivered following daily prostate localization using on-board kV imaging (OBI) to localize gold seed fiducial markers within the prostate. Acute and late toxicities were graded as per the NCI CTCAEv3.0. The median follow-up was 22 months. The magnitude and direction of prostate displacement and daily shifts in three axes are reported. Of note, 9.1% and 12.9% of prostate displacements were ≥ 5 mm in the anterior-posterior and superior-inferior directions, respectively. Acute grade 2 GI and GU events occurred in 11% and 39% of patients, respectively, however no grade 3 or higher acute GI or GU events were observed. Regarding late toxicity, 2% and 17% of patients developed grade 2 toxicities, and similarly no grade 3 or higher events had occurred by last follow-up. Thus, kV imaging detected a substantial amount of inter-fractional displacement and may help reduce toxicity profiles, especially high grade events, by improving the accuracy of dose delivery.
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Neoplasias de la Próstata/radioterapia , Traumatismos por Radiación/patología , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Anciano , Anciano de 80 o más Años , Imagen Eco-Planar , Marcadores Fiduciales , Tracto Gastrointestinal/efectos de la radiación , Humanos , Masculino , Persona de Mediana Edad , Traumatismos por Radiación/etiología , Estudios Retrospectivos , Sistema Urogenital/efectos de la radiaciónRESUMEN
The potential shape memory alloy Ni(50)Mn(34)In(16) is studied with partial substitution of Mn with Fe and Cr to investigate the effect of such substitution on the martensitic transition in the Ni-Mn-In alloy system. The results of ac susceptibility, magnetization and electrical resistivity measurements show that while the substitution with Cr increases the martensitic transition temperature, the substitution with Fe decreases it. Possible reasons for this shift in martensitic transition are discussed. Evidence of kinetic arrest of the austenite to martensite phase transition in the Fe substituted alloys is also presented. Unlike the kinetic arrest of the austenite to martensite phase transition in the parent Ni(50)Mn(34)In(16) alloy which takes place in the presence of high external magnetic field, the kinetic arrest of the austenite to martensite phase transition in the Fe doped alloy occurs even in zero magnetic field. The Cr substituted alloys, on the other hand, show no signature of kinetic arrest of this phase transition.
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Systemic lupus erythematosus (SLE) is an autoimmune disease with highly variable clinical presentation. Patients suffer from immunological abnormalities that target T-cell, B-cell and accessory cell functions. B cells are hyperactive in SLE patients. An adapter protein expressed in B cells called BANK1 (B-cell scaffold protein with ankyrin repeats) was reported in a previous study to be associated with SLE in a European population. The objective of this study was to assess the BANK1 genotype-phenotype association in an independent replication sample. We genotyped 38 single nucleotide polymorphisms (SNPs) in BANK1 on 1892 European-derived SLE patients and 2652 European-derived controls. The strongest associations with SLE and BANK1 were at rs17266594 (corrected P-value=1.97 x 10(-5), odds ratio (OR)=1.22, 95% CI 1.12-1.34) and rs10516487 (corrected P-value=2.59 x 10(-5), OR=1.22, 95% CI 1.11-1.34). Our findings suggest that the association is explained by these two SNPs, confirming previous reports that these polymorphisms contribute to the risk of developing lupus. Analysis of patient subsets enriched for hematological, immunological and renal ACR criteria or the levels of autoantibodies, such as anti-RNP A and anti-SmRNP, uncovers additional BANK1 associations. Our results suggest that BANK1 polymorphisms alter immune system development and function to increase the risk for developing lupus.
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Proteínas Adaptadoras Transductoras de Señales/genética , Predisposición Genética a la Enfermedad , Lupus Eritematoso Sistémico/genética , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Proteínas Adaptadoras Transductoras de Señales/inmunología , Estudios de Casos y Controles , Humanos , Lupus Eritematoso Sistémico/inmunología , Proteínas de la Membrana/inmunología , Población Blanca/genéticaRESUMEN
We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case-control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P=1.1 x 10(-4), odds ratio (OR)=0.81 (95% confidence interval: 0.73-0.90)). This single nucleotide polymorphism (SNP) is located in the 5' untranslated region within the first intron near the transcription initiation site of LYN. In addition, SNPs upstream of the first exon also show weak and sporadic association in subsets of the total European-American population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for systemic lupus erythematosus (SLE) susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European-American female cases by American College of Rheumatology classification criteria shows a reduction in the risk of hematological disorder with rs6983130 compared with cases without hematological disorders (P=1.5 x 10(-3), OR=0.75 (95% CI: 0.62-0.89)). None of the 90 SNPs tested show significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.
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Lupus Eritematoso Sistémico/genética , Polimorfismo de Nucleótido Simple , Familia-src Quinasas/genética , Factores de Edad , Estudios de Casos y Controles , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/inmunologíaRESUMEN
Systemic Lupus Erythematosus (SLE) disproportionately affects minorities, such as Hispanic Americans (HA). Prevalence of SLE is 3-5 times higher in HA than in European-derived populations and have more active disease at the time of diagnosis, with more serious organ system involvement. HA is an admixed population, it is possible that there is an effect of admixture on the relative risk of the disease. This admixture can create substantial increase of linkage disequilibrium (LD) in both magnitude and range, which can provide a unique opportunity for admixture mapping. The main objectives of this study are to (a) estimate hidden population structure in HA individuals; (b) estimate individual ancestry proportions and its impact on SLE risk; (c) assess impact of admixture on ITGAM association, a recently identified SLE susceptibility gene; and (d) estimate power of admixture mapping in HA. Our dataset contained 1125 individuals, of whom 884 (657 SLE cases and 227 controls) were self-classified as HA. Using 107 unlinked ancestry informative markers (AIMs), we estimated hidden population structure and individual ancestry in HA. Out of 5671 possible pairwise LD, 54% were statistically significant, indicating recent population admixture. The best-fitted model for HA was a four-population model with average ancestry of European (48%), American-Indian (AI) (40%), African (8%) and a fourth population (4%) with unknown ancestry. We also identified significant higher risk associated with AI ancestry (odds ratio (OR)=4.84, P=0.0001, 95% CI (confidence interval)=2.14-10.95) on overall SLE. We showed that ITGAM is associated as a risk factor for SLE (OR=2.06, P=8.74 x 10(-5), 95% CI=1.44-2.97). This association is not affected by population substructure or admixture. We have shown that HA have great potential and are an appropriate population for admixture mapping. As expected, the case-only design is more powerful than case-control design, for any given admixture proportion or ancestry risk ratio.
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Antígeno CD11b/genética , Hispánicos o Latinos/genética , Lupus Eritematoso Sistémico/etnología , Lupus Eritematoso Sistémico/genética , Etnicidad/genética , HumanosRESUMEN
Few large, multi-ethnic studies have examined the clinical and serologic differences between familial and sporadic SLE patients. Understanding these similarities and differences is critical for interpreting genetic studies and developing therapeutic strategies. We compiled information on 1915 patients with SLE in a large multi-racial cohort, including general demographics, pedigree structure and the specific American College of Rheumatology (ACR) criteria met. One patient was randomly selected from each multiplex family for analysis, yielding 554 European-Americans (EA), 373 African-Americans (AA), 193 Hispanics (HI) and 237 patients of other of mixed races. When comparing familial and sporadic patients stratified by race, lupus erythematosus (LE) cells and arthritis were increased in white familial cases (P = 5.5 x 10(-6) and P = 0.028, respectively), but no other significant differences between familial and sporadic patients were found. We found that there were profound differences in clinical profiles between races. For example, photosensitivity and malar rash were decreased in AA (P = 1.3 x 10(-13) and 1.4 x 10(-7), respectively), whereas discoid rash was increased in AA (P = 5.5x10(-6)). EA had significantly less renal disease (P = 5.4x10(-13)), proteinuria (P = 4 x 10(-12)) and anti-Sm (P = 1.7 x 10(-12)) than AA or HI. We, therefore, conclude that familial and sporadic onset patients may be treated similarly with respect to clinical and genetic studies.
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Negro o Afroamericano , Hispánicos o Latinos , Lupus Eritematoso Sistémico/genética , Población Blanca , Adulto , Femenino , Humanos , MasculinoRESUMEN
Recently, the transcription factor-7-like 2 (TCF7L2) gene has been identified as the most important type 2 diabetes mellitus (T2DM) susceptibility gene. Common intronic polymorphisms in this gene have been found to be strongly associated with T2DM susceptibility showing marked reproducibility in multiple populations. The purpose of this study was to confirm the reported association of six TCF7L2 variants in a Khatri Sikh diabetic sample from North India. We genotyped six-associated SNPs in a case-control sample consisting of 556 T2DM cases and 537 controls. We also examined the impact of these variants on body mass index (BMI), waist to hip ratio (WHR), fasting insulin, and glucose and lipid levels. We report replication of association of four of the six SNPs with T2DM in this Khatri Sikh sample [rs7903146, (p = 0.010); rs11196205, (p = 0.011); rs10885409, (p = 0.002) and rs4918789, (p = 0.029)], under a dominant model conferring odds ratios (ORs) of 1.39, 1.44, 1.57 and 1.36, respectively. Haplotype analysis provided further evidence of association by showing a significant difference between cases and controls as revealed by the global omnibus test (chi(2)= 19.36; p = 0.0036). Multiple linear regression analysis also revealed the risk allele carriers of three of four significant SNPs (rs7903146, rs11196205, rs10885409) to be significantly associated with increased fasting total cholesterol (p value = 0.019, 0.025, 0.006) and LDL cholesterol levels (p value = 0.021, 0.018, 0.005), respectively. Our findings confirm that the TCF7L2 gene is a major risk factor for development of T2DM in Khatri Sikhs. It also provides new information about the significant impact of TCF7L2 gene variants on plasma cholesterol levels that appear to be independent of BMI.
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Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Variación Genética , Lípidos/sangre , Polimorfismo de Nucleótido Simple , Factores de Transcripción TCF/genética , Adulto , Anciano , Glucemia , Índice de Masa Corporal , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Haplotipos , Humanos , India , Insulina/sangre , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores de Transcripción TCF/metabolismo , Proteína 2 Similar al Factor de Transcripción 7RESUMEN
OBJECTIVE: Two novel non-synonymous polymorphisms of the APRIL gene, codon 67 (rs11552708) and 96 (rs3803800), were recently identified and tested for disease association. The 67G allele was reported to be associated with systemic lupus erythematosus (SLE) in a Japanese population. The aim of the study is to investigate whether the APRIL polymorphism associated with susceptibility to SLE in a Japanese population is associated with the susceptibility to SLE in other ethnic groups. METHODS: Three hundred and forty-eight SLE patients (204 European-American, 103 African-American and 41 Hispanic) and 345 ethnicity-matched controls (201 European-American, 104 African-American and 40 Hispanic) were included from the Lupus Multiplex Registry and Repository (LMRR) and evaluated for genetic association. The APRIL codon 67 and codon 96 were genotyped by a 3-base extension method. Statistical evaluations were performed using both chi-square and logistic regression analysis. RESULTS: Both the single-nucleotide polymorphisms (SNPs) were in Hardy-Weinberg equilibrium in cases and controls within each ethnic group. The APRIL codon 67 was significantly associated with SLE risk under the dominant model adjusted by ethnicity (odds ratio, 95% confidence interval and P-values were 1.45 and 1.02-2.06 and 0.036, respectively). Race-specific analysis also showed a trend for association in African-American and Hispanic SLE subjects. CONCLUSION The APRIL codon G67R polymorphism associated with SLE in a Japanese population may also be associated with SLE in other populations.
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Lupus Eritematoso Sistémico/genética , Polimorfismo de Nucleótido Simple , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genética , Negro o Afroamericano/estadística & datos numéricos , Estudios de Casos y Controles , Europa (Continente)/etnología , Femenino , Predisposición Genética a la Enfermedad , Haplotipos , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Lupus Eritematoso Sistémico/etnología , Masculino , Oklahoma/epidemiologíaRESUMEN
OBJECTIVE: To assess whether combined evidence shows the association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) C1858T polymorphism and autoimmune diseases, and to summarize the effect size of the polymorphism associated with susceptibility of autoimmune diseases. METHODS: We surveyed studies on the PTPN22 C1858T polymorphism and autoimmune diseases using comprehensive Medline search and review of the references. Meta-analysis was performed for genotypes T/T (recessive effect), T/T + C/T (dominant effect) and T-allele in random effects models. RESULTS: Twenty-nine studies with 43 comparisons including 13 rheumatoid arthritis (RA), six systemic lupus erythematosus (SLE), six type-1 DM (T1D), three Grave's disease (GD), four inflammatory bowel diseases (IBD), three juvenile idiopathic arthritis (JIA), two psoriasis, two multiple sclerosis, two Addison's disease and two Celiac disease were available for the meta-analysis. The overall odds ratios (ORS) for T-allele, T/T and T/T + C/T genotypes were significantly increased in RA, SLE, GD and T1D (OR for T-allele = 1.58, 1.49, 1.85, 1.61, respectively, P < 0.00001). This meta-analysis showed the association between the T-allele and the T/T genotype and JIA (OR = 1.34, P = 0.03; OR = 1.97, P = 0.02) but did not reveal the association between the PTPN22 C1858T polymorphism and IBD, psoriasis, multiple sclerosis, Addison's disease and Celiac disease. CONCLUSION: This meta-analysis demonstrates that the PTPN22 1858T allele confers susceptibility to RA, SLE, GD, T1D and JIA, supporting evidence of association of the PTPN22 gene with subgroup of autoimmune diseases.
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Enfermedades Autoinmunes/genética , Polimorfismo de Nucleótido Simple , Proteínas Tirosina Fosfatasas/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Proteína Tirosina Fosfatasa no Receptora Tipo 22 , Enfermedades Reumáticas/genéticaRESUMEN
We detected a novel susceptibility gene, SLER1, for systemic lupus erythematosus (SLE) at 5p15.3.(1) This finding was based on a selected subgroup of SLE families, where two or more family members have had alleged rheumatoid arthritis (SLE-RA). The main objective of this study was to replicate the linkage at 5p15.3 based on an independent data set of 88 SLE-RA families. Heterogeneity in the genetic model led us to use a nonparametric allele-sharing method. Since our a priori hypothesis of linkage at 5p15.3 was fixed, we genotyped six markers at the linked region. Our new results replicate the initial linkage at 5p15.3 (Zlr=2.58, P<0.005, LOD=1.45). Moreover, evidence of linkage was sustained when analysis was restricted to the subset of SLE families who had 3 or more individuals with alleged RA (Zlr=3.32, P=0.008, LOD=2.40) The results of our previous findings, together with these new results, confirm the SLER1 linkage at 5p15.3. Our results also demonstrate the utility of clinically defined subgroup analysis for detecting susceptibility loci for complex genetic diseases, such as SLE.
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Cromosomas Humanos Par 5/genética , Ligamiento Genético/genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad/genética , Lupus Eritematoso Sistémico/genética , Secuencias Repetidas en Tándem/genética , Artritis Reumatoide/genética , Estudios de Cohortes , Femenino , Genotipo , Humanos , Escala de Lod , Masculino , LinajeRESUMEN
Systemic lupus erythematosus (SLE) is an autoimmune disease with complex genetics. We evaluated pedigrees multiplex for SLE that had an affected with antinucleolar antibodies to increase the homogeneity for genetic linkage analysis. We found a significant linkage effect on chromosome 11q14 at marker D11S2002 in African-American Pedigrees. This effect produced a maximum LOD score of 5.62 using a dominant inheritance model with 95% penetrance in males and 99% penetrance in females. The results were supported by multipoint linkage analysis. Fine mapping of the region with two additional markers within 6 cM of D11S2002 further provided evidence of linkage in this region. Linkage at D11S2002, named SLEH1, was previously found in some of these same African-American pedigrees multiplex for SLE, but who were stratified by hemolytic anemia (Kelly et al, submitted). In conclusion, an important SLE susceptibility gene, SLEH1 at 11q14, is identified in African-Americans when stratifying pedigrees by antinucleolar autoantibodies.
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Nucléolo Celular/inmunología , Cromosomas Humanos Par 11 , Lupus Eritematoso Sistémico/genética , Población Negra/genética , Femenino , Técnica del Anticuerpo Fluorescente , Ligamiento Genético , Humanos , Escala de Lod , Masculino , Repeticiones de Microsatélite , Modelos Genéticos , Linaje , Población Blanca/genéticaRESUMEN
Anti-double-stranded DNA (anti-dsDNA) is arguably one of the most specific autoantibodies in systemic lupus erythematosus (SLE). This antibody is associated with more severe SLE and with glomerulonephritis. From 196 pedigrees multiplex for SLE, we selected those that had any SLE affected positive for anti-dsDNA by the Crithidia luciliae kinetoplast imunofluorescence assay. This stratification strategy tested the hypothesis that anti-dsDNA would identify a more genetically homogeneous group of pedigrees, in which previously undetected linkage effects could be established. A genome screen data for linkage to SLE was available at 307 microsatellite markers for this selected group of 71 pedigrees: 37 European-American, 29 African-American, and five others. The most significant results were obtained at 19p13.2 (LOD(max) = 4.93), named SLED1, in the 37 European-American pedigrees using a dominant model with mixed penetrances (92% for females and 49% for males) at 100% homogeneity (theta = 0). A second linkage effect, SLED2, was established in the 29 African-American pedigrees at 18q21.1 (LOD(max) = 3.40) using a recessive model with 100% penetrance (theta = 0.1). Parametric and non-parametric multipoint analyses were performed, which provided further evidence and support of susceptibility genes residing in these regions. In conclusion, two powerful linkages have been detected with SLE based on the presence of anti-dsDNA. These findings show SLE to be a richly complicated disease phenotype that is now ripe for important new discovery through a genetic approach.
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Autoanticuerpos/inmunología , Cromosomas Humanos Par 18 , Cromosomas Humanos Par 19 , ADN/inmunología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Animales , Anticuerpos/sangre , Crithidia/inmunología , Femenino , Técnica del Anticuerpo Fluorescente , Ligamiento Genético , Humanos , Escala de Lod , Masculino , LinajeRESUMEN
Both systemic lupus erythematosus (SLE) and vitiligo are autoimmune disorders that have strong evidence of complex genetic contributions to their etiology, but, to date, efforts using genetic linkage to find the susceptibility genes for either phenotype have met with limited success. Since autoimmune diseases are thought to share at least some of their genetic origins, and since only a small minority (16 of 92) of the European-American pedigrees multiplex for SLE in our collection have one or more affected members with vitiligo, we hypothesized that these pedigrees might be more genetically homogeneous at loci important to both SLE and vitiligo and, hence, have increased power for detection of linkage. We therefore evaluated genomewide microsatellite-marker-scan data for markers at an average marker density of approximately 11 cM in these 16 European-American pedigrees and identified a significant linkage at 17p13, where the maximum multipoint parametric LOD score was 3.64 (P<4.3x10(-5)) and the nonparametric linkage score was 4.02 (P<2.8x10(-5)), respectively. The segregation behavior of this linkage suggests a recessive mode of inheritance with a virtually homogeneous genetic effect in these 16 pedigrees. These results support the hypotheses that SLE and vitiligo may share important genetic effects and that sampling on the basis of clinical covariates dramatically improves power to identify genetic effects.
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Cromosomas Humanos Par 17/genética , Predisposición Genética a la Enfermedad/genética , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/genética , Mutación/genética , Vitíligo/complicaciones , Vitíligo/genética , Mapeo Cromosómico , Femenino , Genes , Humanos , Escala de Lod , Masculino , Repeticiones de Microsatélite/genética , LinajeRESUMEN
A genome-wide search was conducted to identify chromosomal regions likely to harbor genes for asthma susceptibility. One hundred and twelve Caucasian families ascertained through a proband with a diagnosis of asthma by the Collaborative Study on the Genetics of Asthma (CSGA) were used for this search. Genotype data on 323 polymorphic markers were analyzed via parametric and nonparametric linkage analysis in an initial genome scan to identify potential asthma susceptibility region(s). The regions where hold or nonparametric linkage scores were greater than 2.0 were selected for further investigation using two-trait-locus linkage analysis models.