RESUMO
INTRODUCTION: Renal transplantation is the optimal renal replacement therapy. In Mexico, most of the kidney transplants are from living donors. It is essential to identify conditions that increase the risk of developing chronic kidney disease (CKD) in donors, such as metabolic syndrome (MS). MATERIALS AND METHODS: In retrospect from January 2008 to December 2018, the donation protocols for renal transplantation of the Hospital Central Sur Alta Especialidad "Picacho" were reviewed, classifying all the cases of donors by nephrectomy or no nephrectomy and describing the demographic characteristics, prevalence of metabolic diseases, and cause of rejection of the protocol. RESULTS: A total of 178 donors were studied: 82 women (46%), 96 men (54%), mean age of 42 years, average body mass index (BMI) 27.9 kg/m2, glomerular filtration rate (GFR) by Chronic Kidney Disease Epidemiology Collaboration 99 mL/min, 59 patients with grade I and II obesity (BMI ≥ 30 kg/m2), and 1 patient with morbid obesity (BMI ≥ 40 kg/m2). A total of 39 patients (22%) underwent nephrectomy and 139 (78%) did not. The following characteristics and alterations were found: Of the 139 patients who did not undergo nephrectomy, 91 had metabolic disorders, 20 had low GFR, 21 had albuminuria, and 4 recipients received cadaveric transplants, 3 due to critical conditions of the recipient. The metabolic alterations in the rejected donors were as follows: MS 54 (59%), prediabetes 55 (39%), newly diagnosed hypertension 70 (76%), diabetes mellitus 20 (14%), obesity 47 (51.6%), dyslipidemia 76 (83%), hyperuricemia 17 (12%). DISCUSSION: The prevalence of MS in apparently healthy donors is similar to that of other studies in Mexico. Both MS and its components are independently associated with an increased risk of cardiovascular disease and CKD. It has been shown that these donors have a greater degree of glomerular and interstitial fibrosis; therefore, diagnosis, prevention, and timely treatment in this group are important.
Assuntos
Transplante de Rim , Doadores Vivos , Síndrome Metabólica/epidemiologia , Adulto , Feminino , Humanos , Transplante de Rim/métodos , Doadores Vivos/provisão & distribuição , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
Bipolar disorder and alcohol use disorder (AUD) have a high rate of comorbidity, more than 50% of individuals with bipolar disorder also receive a diagnosis of AUD in their lifetimes. Although both disorders are heritable, it is unclear if the same genetic factors mediate risk for bipolar disorder and AUD. We examined 733 Costa Rican individuals from 61 bipolar pedigrees. Based on a best estimate process, 32% of the sample met criteria for bipolar disorder, 17% had a lifetime AUD diagnosis, 32% met criteria for lifetime nicotine dependence, and 21% had an anxiety disorder. AUD, nicotine dependence and anxiety disorders were relatively more common among individuals with bipolar disorder than in their non-bipolar relatives. All illnesses were shown to be heritable and bipolar disorder was genetically correlated with AUD, nicotine dependence and anxiety disorders. The genetic correlation between bipolar and AUD remained when controlling for anxiety, suggesting that unique genetic factors influence the risk for comorbid bipolar and AUD independent of anxiety. Our findings provide evidence for shared genetic effects on bipolar disorder and AUD risk. Demonstrating that common genetic factors influence these independent diagnostic constructs could help to refine our diagnostic nosology.
Assuntos
Transtornos Relacionados ao Uso de Álcool/genética , Transtorno Bipolar/genética , Predisposição Genética para Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Transtorno Bipolar/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Adulto JovemRESUMO
Only a few cases of complete atrioventricular block (AVB) in adult lupus patients have been previously described, but only one as the initial manifestation. A 19-year-old woman who presented with seizures and loss of consciousness, was diagnosed with complete ABV and underwent pacemaker placement. Over the next weeks she developed serositis, joint, cutaneous, and renal involvement; positive antinuclear antibodies and high anti-SSA/Ro titers. This is the second case with AVB as a feature of SLE at onset. A review of previous complete AVB cases of adult SLE patients is presented.
Assuntos
Bloqueio Atrioventricular/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Feminino , Humanos , Adulto JovemRESUMO
Schizophrenia (SC) and bipolar disorder (BP) share many clinical features, among them psychosis. We previously identified a putative gene locus for psychosis on chromosome 18p in a sample from the Central Valley of Costa Rica (CVCR) population. The present study replicated the association to a specific allele of microsatellite marker D18S63 on 18p11.3, using a newly collected sample from the CVCR. A combined analysis of both samples, plus additional subjects, showed that this specific allele on D18S63, which lies within an intron on the TGFB-induced factor (TGIF) gene, is strongly associated (P-value=0.0005) with psychosis. Eleven additional SNP markers, spanning five genes in the region, were analyzed in the combined sample from the CVCR. Only the four SNPs within the TGIF gene were in strong linkage disequilibrium with D18S63 (D'=1.00). A specific haplotype for all five markers within the TGIF gene showed evidence of association (P-value=0.011) to psychosis. A second, distinct haplotype, containing a newly identified nonsynonymous polymorphism in exon 5 of the TGIF gene, showed a nonsignificant trend towards association to psychosis (P-value=0.077). TGIF is involved in neurodevelopment, neuron survival and controls the expression of dopamine receptors. Altogether, our results point to the possible involvement of TGIF in the pathophysiology of psychotic disorders in the CVCR population.
Assuntos
Cromossomos Humanos Par 18 , Predisposição Genética para Doença , Proteínas de Homeodomínio/genética , Polimorfismo Conformacional de Fita Simples , Transtornos Psicóticos/genética , Proteínas Repressoras/genética , Alelos , Animais , Mapeamento Cromossômico , Costa Rica , Análise Mutacional de DNA , Saúde da Família , Feminino , Frequência do Gene , Humanos , Desequilíbrio de Ligação , MasculinoRESUMO
Schizophrenia is a complex psychiatric disorder, likely to be caused in part by multiple genes. In this study, linkage analyses were performed to identify chromosomal regions most likely to be associated with schizophrenia and psychosis in multiplex families of Mexican and Central American origin. Four hundred and fifty-nine individuals from 99 families, containing at least two siblings with hospital diagnoses of schizophrenia or schizoaffective disorder, were genotyped. Four hundred and four microsatellite markers were genotyped for all individuals and multipoint non-parametric linkage analyses were performed using broad (any psychosis) and narrow (schizophrenia and schizoaffective disorder) models. Under the broad model, three chromosomal regions (1pter-p36, 5q35, and 18p11) exhibited evidence of linkage with non-parametric lod (NPL) scores greater than 2.7 (equivalent to empirical P values of less than 0.001) with the peak multipoint NPL = 3.42 (empirical P value = 0.00003), meeting genomewide evidence for significant linkage in the 1pter-p36 region. Under the narrow model, the same three loci showed (non-significant) evidence of linkage. These linkage findings (1pter-p36, 18p11, and 5q35) highlight where genes for psychosis and schizophrenia are most likely to be found in persons of Mexican and Central American ancestry, and correspond to recent linkages of schizophrenia or psychosis in other populations which were formed in part from emigrants from the Spanish empire of the 15th and 16th centuries.
Assuntos
Predisposição Genética para Doença/genética , Genoma Humano/genética , Linhagem , Transtornos Psicóticos/genética , Esquizofrenia/genética , América Central/etnologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Ligação Genética , Humanos , México/etnologia , Fenótipo , Estatísticas não ParamétricasRESUMO
OBJECTIVE: This study used the population of the Central Valley of Costa Rica (CVCR) and phenotyping strategies alternative to DSMIV classifications to investigate the association of neuregulin 1 with schizophrenia. METHOD: Using 134 family trios with a history of psychosis, we genotyped six of the seven markers originally identified to be associated with schizophrenia in Iceland. RESULTS: The neuregulin Icelandic haplotype was not associated with schizophrenia in the CVCR population. However, a novel haplotype was found to be overrepresented in subjects with functional psychosis (global P-value > 0.05). Stratification of the sample by history of mania suggests that this haplotype may be preferentially over-transmitted to persons with a history of manic psychosis. CONCLUSION: These results suggest that the neuregulin 1 gene is unlikely to play a major role in predisposing to schizophrenia in the CVCR. Further studies in the CVCR and other Latin American populations should be performed in order to corroborate these findings.
Assuntos
Transtorno Bipolar/etnologia , Transtorno Bipolar/genética , Hispânico ou Latino/genética , Hispânico ou Latino/estatística & dados numéricos , Proteínas do Tecido Nervoso/genética , Esquizofrenia/etnologia , Esquizofrenia/genética , Área Programática de Saúde , Costa Rica/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação/genética , Repetições de Microssatélites , Neuregulina-1 , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
We have searched for genes predisposing to bipolar disorder (BP) by studying individuals with the most extreme form of the affected phenotype, BP-I, ascertained from the genetically isolated population of the Central Valley of Costa Rica (CVCR). The results of a previous linkage analysis on two extended CVCR BP-I pedigrees, CR001 and CR004, and of linkage disequilibrium (LD) analyses of a CVCR population sample of BP-I patients implicated a candidate region on 18p11.3. We further investigated this region by creating a physical map and developing 4 new microsatellite and 26 single-nucleotide polymorphism markers for typing in the pedigree and population samples. We report the results of fine-scale association analyses in the population sample, as well as evaluation of haplotypes in pedigree CR001. Our results suggest a candidate region containing six genes but also highlight the complexities of LD mapping of common disorders.
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Transtorno Bipolar/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 18 , Transtornos do Humor/genética , Alelos , Costa Rica , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Masculino , Repetições de Microssatélites/genética , LinhagemRESUMO
Linkage disequilibrium (LD) methods offer great promise for mapping complex traits, but have thus far been applied sparingly. In this paper we describe an LD mapping study of severe bipolar disorder (BP-I) in the genetically isolated population of the Central Valley of Costa Rica. This study provides the first complete screen of a chromosome for a complex trait using LD mapping and presents the first application of a new LD mapping statistic (ancestral haplotype reconstruction (AHR)) that evaluates haplotype sharing among affected individuals. The results of this chromosome-wide analysis are instructive for genome-wide LD mapping in isolated populations. Furthermore, the analysis continues to support a possible BP-I locus on 18pter, suggested by previous analyses in this population. Evidence for a possible BP-I locus on 18q12.2 is also described.
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Transtorno Bipolar/genética , Cromossomos Humanos Par 18 , Desequilíbrio de Ligação , Costa Rica , Seguimentos , Marcadores Genéticos , Genótipo , Haplótipos , Humanos , Modelos GenéticosRESUMO
OBJECTIVES: Population isolates offer several advantages for those hoping to identify predisposition genes for bipolar disorder (BP). In this review article, the rationale for performing gene mapping studies in this type of population and the results of genetic mapping studies performed to date in population isolates are presented. METHODS: This article begins with a brief review of the concepts involved in mapping genes for BP. The concept of populations that show some degree of historical isolation and their special utility for certain types of gene mapping is presented. Methods of statistical analysis particularly relevant for gene mapping of complex diseases like BP are presented. Finally, several BP gene studies conducted to date in several population isolates are reviewed. RESULTS: Genetic mapping studies of BP have occurred thus far in several isolates or sub-isolates, including the Amish population, Costa Ricans, Finnish, and Canadians (in Quebec), and significant linkage scores have been identified in the latter three isolates. CONCLUSIONS: Possible greater homogeneity and greater consistency of diagnosis are factors that have been cited in several studies of BP done in isolates to date. Another special advantage of working in certain types of population isolate is their appropriateness for using certain types of association or linkage disequilibrium-based approaches at both the genome screening and fine mapping stages. These tests include mapping by linkage disequilibrium analyses, an approach that allows mapping to occur at the population, rather than the pedigree, level.
Assuntos
Transtorno Bipolar/genética , Expressão Gênica/genética , Transtorno Bipolar/epidemiologia , Canadá/epidemiologia , Costa Rica/epidemiologia , Humanos , Islândia/epidemiologia , Judeus/estatística & dados numéricos , Desequilíbrio de Ligação , Escócia/epidemiologiaRESUMO
Acheiropodia is an autosomal recessive disease that results in hemimelia (lack of formation of the distal extremities). We performed a complete genome screen of seven members of an extended pedigree that included three siblings with acheiropodia. Homozygosity mapping was used to identify regions most likely to harbor the gene for acheiropodia in this pedigree. In these two key regions (14p and 7q), further genotyping of one additional affected member of this pedigree plus seven additional unaffected siblings provided evidence, through linkage analysis, that the 7q36 region contains the acheiropodia gene. In this region, a maximum two-point LOD score of 3.81 (4.2 with multipoint analysis) was achieved, and a homozygous haplotype spanning a region of 11.7 cM was seen in all affected in this pedigree. Finally, genotypic analysis of two additional cases of acheiropodia with no known relation to the other samples revealed homozygous sharing of a portion of the same haplotype on 7q36, which reduces the chromosomal location of the acheiropodia gene to an 8.6-cM region. Localization of this gene, at the screening level, by use of data from only three affected subjects, provides an example of how certain genes may be mapped by use of a minimal number of affected cases.
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Mapeamento Cromossômico/métodos , Ectromelia/genética , Homozigoto , Brasil , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 7/genética , Feminino , Haplótipos/genética , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Núcleo Familiar , Linhagem , Polimorfismo Genético/genéticaRESUMO
Bipolar mood disorder (BP) is a debilitating syndrome characterized by episodes of mania and depression. We designed a multistage study to detect all major loci predisposing to severe BP (termed BP-I) in two pedigrees drawn from the Central Valley of Costa Rica, where the population is largely descended from a few founders in the 16th-18th centuries. We considered only individuals with BP-I as affected and screened the genome for linkage with 473 microsatellite markers. We used a model for linkage analysis that incorporated a high phenocopy rate and a conservative estimate of penetrance. Our goal in this study was not to establish definitive linkage but rather to detect all regions possibly harboring major genes for BP-I in these pedigrees. To facilitate this aim, we evaluated the degree to which markers that were informative in our data set provided coverage of each genome region; we estimate that at least 94% of the genome has been covered, at a predesignated threshold determined through prior linkage simulation analyses. We report here the results of our genome screen for BP-I loci and indicate several regions that merit further study, including segments in 18q, 18p, and 11p, in which suggestive lod scores were observed for two or more contiguous markers. Isolated lod scores that exceeded our thresholds in one or both families also occurred on chromosomes 1, 2, 3, 4, 5, 7, 13, 15, 16, and 17. Interesting regions highlighted in this genome screen will be followed up using linkage disequilibrium (LD) methods.
Assuntos
Transtorno Bipolar/genética , Cromossomos Humanos Par 18 , Genoma Humano , Mapeamento Cromossômico , Costa Rica , Feminino , Genes Dominantes , Ligação Genética , Marcadores Genéticos , Humanos , Escore Lod , Masculino , Repetições de Microssatélites , Modelos Genéticos , LinhagemRESUMO
Linkage disequilibrium (LD) analysis provides a powerful means for screening the genome to map the location of disease genes, such as those for bipolar disorder (BP). As described in this paper, the population of the Central Valley of Costa Rica, which is descended from a small number of founders, should be suitable for LD mapping; this assertion is supported by reconstruction of extended haplotypes shared by distantly related individuals in this population suffering low-frequency hearing loss (LFHL1), which has previously been mapped by linkage analysis. A sampling strategy is described for applying LD methods to map genes for BP, and clinical and demographic characteristics of an initially collected sample are discussed. This sample will provide a complement to a previously collected set of Costa Rican BP families which is under investigation using standard linkage analysis.
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Transtorno Bipolar/genética , Mapeamento Cromossômico , Desequilíbrio de Ligação , Adulto , Transtorno Bipolar/epidemiologia , Costa Rica/epidemiologia , Feminino , Haplótipos , Perda Auditiva/genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Manic depressive illness, or bipolar disorder (BP), is characterized by episodes of elevated mood (mania) and depression. We designed a multistage study in the genetically isolated population of the Central Valley of Costa Rica to identify genes that promote susceptibility to severe BP (termed BPI), and screened the genome ot two Costa Rican BPI pedigrees (McInnes et al., submitted). We considered only individuals who fulfilled very stringent diagnostic criteria for BPI to be affected. The strongest evidence for a BPI locus was observed in 18q22-q23. We tested 16 additional markers in this region and seven yielded peak lod scores over 1.0. These suggestive lod scores were obtained over a far greater chromosomal length (about 40 cM) than in any other genome region. This localization is supported by marker haplotypes shared by 23 of 26 BPI affected individuals studied. Additionally, marker allele frequencies over portions of this region are significantly different in the patient sample from those of the general Costa Rican population. Finally, we performed an analysis which made use of both the evidence for linkage and for association in 18q23, and we observed significant lod scores for two markers in this region.