RESUMEN
Recent genome-wide association studies have identified many loci associated with type 2 diabetes mellitus (T2DM), hyperuricemia, and obesity in various ethnic populations. However, quantitative traits have been less well investigated in Han Chinese T2DM populations. We investigated the association between candidate gene single nucleotide polymorphisms (SNPs) and metabolic syndrome-related quantitative traits in Han Chinese T2DM subjects. Unrelated Han Chinese T2DM patients (1975) were recruited. Eighty-six SNPs were genotyped and tested for association with quantitative traits including lipid profiles, blood pressure, body mass index (BMI), serum uric acid (SUA), glycated hemoglobin (HbA1c), plasma glucose [fasting plasma glucose (FPG)], plasma glucose 120 min post-OGTT (P2PG; OGTT = oral glucose tolerance test), and insulin resistance-related traits. We found that CAMTA1, ABI2, VHL, KAT2B, PKHD1, ESR1, TOX, SLC30A8, SFI1, and MYH9 polymorphisms were associated with HbA1c, FPG, and/or P2PG; GCK, HHEX, TCF7L2, KCNQ1, and TBX5 polymorphisms were associated with insulin resistance-related traits; ABCG2, SLC2A9, and PKHD1 polymorphisms were associated with SUA; CAMTA1, VHL, KAT2B, PON1, NUB1, SLITRK5, SMAD3, FTO, FANCA, and PCSK2 polymorphisms were associated with blood lipid traits; CAMTA1, SPAG16, TOX, KCNQ1, ACACB, and MYH9 polymorphisms were associated with blood pressure; and UBE2E3, SPAG16, SLC2A9, CDKAL1, CDKN2A/B, TCF7L2, SMAD3, and PNPLA3 polymorphisms were associated with BMI (all P values <0.05). Some of the candidate genes were associated with metabolic and anthropometric traits in T2DM in Han Chinese. Although none of these associations reached genome-wide significance (P < 5 x 10(-8)), genes and loci identified in this study are worthy of further replication and investigation.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Carácter Cuantitativo Heredable , Anciano , Metabolismo Energético/genética , Femenino , Humanos , Resistencia a la Insulina/genética , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
We identified three novel mutations of the GTP cyclohydrolase 1 (GCH1) gene in patients with familial dopa-responsive dystonia (DRD), but were unable to identify meaningful sporadic mutations in patients with no obvious family DRD background. To investigate whether GCH1 regional deletions account for the etiology of DRD, we screened for heterozygous exonic deletions in DRD families and in patients with sporadic DRD. Multiple ligation-dependent probe amplification analysis and quantitative real-time polymerase chain reaction amplification was performed in all members of our DRD cohort and in controls to detect exonic deletions in GCH1, tyrosine hydroxylase, and the epsilon-sarcoglycan-encoding (SGCE) genes. Using these techniques, we detected a GCH1 exon 1 heterozygous deletion in 1 of 10 patients with sporadic DRD. Therefore, we concluded that exonic deletion in the GCH1 gene only accounted for the etiology in a small percentage of patients with sporadic DRD in our Han Chinese cohort.
Asunto(s)
Trastornos Distónicos/genética , GTP Ciclohidrolasa/genética , Pueblo Asiatico/genética , Análisis Mutacional de ADN , Exones , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Masculino , Linaje , Eliminación de SecuenciaRESUMEN
Genetic factors play an important role in type 2 diabetes (T2D) complications. Alteration of cerebrovascular blood flow (CBF) is a direct result of cerebrovascular diseases. However, few studies have reported the role of genetics on CBF in patients with T2D. We investigated whether single-nucleotide polymorphisms (SNPs) in metabolic disease genes are associated with CBF in patients with T2D. CBF velocities of CBF were measured in 337 Han Chinese patients with T2D using transcranial Doppler sonography, with 54 cerebrovascular blood flow parameters documented. Fifty-two SNPs from 31 metabolic disease candidate genes were genotyped in patients. Quantitative allelic association and haplotype analyses were performed for candidate gene SNPs and CBF phenotypes. Spearman correlation was used to determine the relationship between CBF parameters and basic clinical characteristics, particularly, body mass index, lipids, fibrinogen, and GHbA1c. MYH9 gene SNPs (rs875726 and rs735853) may be associated with the peak velocity of the right-middle cerebral artery. SNPs rs875726, rs2009930, and rs375246 of the MYH9 gene may be associated with the mean velocity of the right-anterior and posterior cerebral artery. The haplotype G-C-A (rs2239782-rs3752462- rs2269532) of MYH9 may be associated with CBF. MYH9 gene polymorphisms may be associated with multiple CBF phenotypes in Chinese patients with T2D. However, whether MYH9 is a candidate gene for cerebrovascular diseases in Chinese patients with T2D remains unknown.
Asunto(s)
Circulación Cerebrovascular/genética , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Proteínas Motoras Moleculares/genética , Cadenas Pesadas de Miosina/genética , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Circulación Cerebrovascular/fisiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Ultrasonografía Doppler TranscranealRESUMEN
Ocular albinism is an X-linked inherited disease characterized by hypopigmentation of the iris and nystagmus. To identify a new disease-causing mutation of ocular albinism, we collected a Han Chinese pedigree with 7 male congenital nystagmus patients over 3 generations. Slit-lamp photography and optical coherence tomography were performed for the proband. Genomic DNA was extracted from a whole blood sample from the proband using the high-salt method. Polymerase chain reaction (PCR) sequencing was carried out for GPR143 and FRMD7 genes. The three-dimensional structures of the wild-type and mutant GPR143 proteins were determined using SWISS-MODEL. The transmission of the disease in the pedigree clearly followed an X-linked pattern. The proband had significant iris and fundus hypopigmentation. Optical coherence tomography showed severe foveal hypoplasias in both eyes of the proband. A novel splicing site (G/C) mutation was found on the boundary of the 6th intron and the 7th exon of the GPR143 gene, resulting in a 9-amino-acid deletion (codons 257-265) in the 6th transmembrane domain of the GPR143 protein. In conclusion, a novel splicing site mutation of the GPR143 gene was found in a Han Chinese congenital ocular albinism pedigree.
Asunto(s)
Albinismo Ocular/genética , Proteínas del Ojo/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Glicoproteínas de Membrana/genética , Mutación , Linaje , Empalme del ARN , Adulto , Albinismo Ocular/diagnóstico , Secuencia de Aminoácidos , Proteínas del Citoesqueleto/genética , Exones , Proteínas del Ojo/química , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Heterocigoto , Humanos , Masculino , Glicoproteínas de Membrana/química , Proteínas de la Membrana/genética , Datos de Secuencia Molecular , Estructura Terciaria de ProteínaRESUMEN
The diversity of specific bacteria taxa, such as the actinomycetes, has not been reported from the Antarctic island of Barrientos. The diversity of actinomycetes was estimated with two different strategies that use PCR-denaturing gradient gel electrophoresis. First, a PCR was applied, using a group-specific primer that allows selective amplification of actinomycete sequences. Second, a nested-PCR approach was used that allows the estimation of the relative abundance of actinomycetes within the bacterial community. Molecular identification, which was based on 16S rDNA sequence analysis, revealed eight genera of actinomycetes, Actinobacterium, Actinomyces, an uncultured Actinomycete, Streptomyces, Leifsonia, Frankineae, Rhodococcus, and Mycobacterium. The uncultured Actinomyces sp and Rhodococcus sp appear to be the prominent genera of actinomycetes in Barrientos Island soil. PCR-denaturing gradient gel electrophoresis patterns were used to look for correlations between actinomycete abundance and environmental characteristics, such as type of rookery and vegetation. There was a significant positive correlation between type of rookery and abundance of actinomycetes; soil samples collected from active chinstrap penguin rookeries had the highest actinomycete abundance. Vegetation type, such as moss, which could provide a microhabitat for bacteria, did not correlate significantly with actinomycete abundance.
Asunto(s)
Actinobacteria/clasificación , Actinobacteria/genética , Microbiología del Suelo , Animales , Regiones Antárticas , Biodiversidad , ADN Bacteriano , ADN Ribosómico/genética , Electroforesis en Gel de Gradiente Desnaturalizante/métodos , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa/métodos , ARN Ribosómico 16S/genética , Suelo/análisis , Spheniscidae/microbiologíaRESUMEN
Expression of the inflammatory isoform of the enzyme nitric oxide synthase (NOS) is increased in airway-lining cells of patients with asthma. The NOS product nitric oxide (NO.) was measured in the expired gas of children with asthma. Vital capacity expirates from 21 control subjects and 13 subjects with asthma were assayed by chemiluminescence. Measurements were highly reproducible (coefficient of variation, 2.6% +/- 1.1%) and did not vary with age, sex, height, or weight. Patients with asthma had mean NO. levels (16.3 parts per billion) that were more than threefold higher than those of control subjects (5.05 ppb; p < 0.001). Expired NO. decreased as airflow obstruction improved during corticosteroid treatment (r2 = 0.77; n = 7; p < 0.001) but remained higher than normal (13.5 ppb; n = 5; p < 0.01) even after airflow obstruction resolved. We demonstrate the use of a reproducible test for asthma in children that is independent of measures of airflow obstruction. We speculate that expired NO assays may prove to be a more sensitive measure of childhood asthma than spirometry.