Pharmacokinetic interaction between pravastatin and olmesartan in relation to SLCO1B1 polymorphism
Abstract
The impact of SLCO1B1 polymorphism on the pharmacokinetics of olmesartan and on the pharmacokinetic interaction between pravastatin and olmesartan was investigated. On day 1, ten healthy volunteers took an oral dose (10 mg) of pravastatin. After a 3-day washout period, each subject received olmesartan medoxomil (10 mg) for 3 days. On day 8, they received olmesartan medoxomil (10 mg) and pravastatin (10 mg) concurrently, and pharmacokinetic profiles were compared with those in each single-dose phase with regard to the SLCO1B1 genotypes (*1b/*1b, *1b/*15, and *15/*15). In the single-dose pha...
Source: Journal of Human Genetics - October 1, 2008 Category: Genetics & Stem Cells Source Type: research
Monozygotic female twins discordant for Silver–Russell syndrome and hypomethylation of the H19-DMR
Abstract
Silver–Russell syndrome (SRS) is characterized by growth failure and dysmorphic features, and is frequently caused by hypomethylation of the paternally derived H19-DMR (epimutation). We observed 5 8/12-year-old female twins discordant for SRS. One twin exhibited SRS-compatible features, such as pre- and postnatal growth failure, relative macrocephaly, triangular face, left hemihypotrophy, and bilateral fifth finger clinodactyly, whereas the other twin showed apparently normal phenotype. Microsatellite analysis for 26 loci on multiple chromosomes showed monozygosity. Methylation analysis for t...
Source: Journal of Human Genetics - October 1, 2008 Category: Genetics & Stem Cells Source Type: research
NEFL Pro22Arg mutation in Charcot-Marie-Tooth disease type 1
In this study, we identified another Pro22 mutation, Pro22Arg, in a Korean CMT1 family. An investigation to identify the clinical and pathological characteristics of the Pro22Arg revealed that it is associated with demyelinating neuropathy features in CMT1F. Histopathological findings showed onion bulb formations but no giant axons. It appears that the Pro22 mutations may influence not only the Thr-Pro phosphorylation site by proline-directed protein kinases but also other structural alteration of the NEFL protein in a different way. (Source: Journal of Human Genetics)
Source: Journal of Human Genetics - October 1, 2008 Category: Genetics & Stem Cells Source Type: research
Case report of de novo dup(18p)/del(18q) and r(18) mosaicism
Abstract
This is a report of a 27-year-old woman with an unusual de novo chromosomal abnormality. Mosaicism was identified in peripheral blood cells examined by standard G-bands by trypsin using Giemsa (GTG) analysis and fluorescence in situ hybridization (FISH) analysis with chromosome-18 region-specific probes, 46,XX,del(18)(pter → q21.33:)[41], 46,XX,r(18)(::p11.21 → q21.33::)[8], and 46,XX,der(18)(pter → q21.33::p11.21 → pter)[1]. On the other hand, the karyotype of periodontal ligament fibroblasts was nonmosaic, 46,XX, der(18)(pter → q21.33::p11.21 → pter)[50]. All cell line...
Source: Journal of Human Genetics - October 1, 2008 Category: Genetics & Stem Cells Source Type: research
Appropriate data cleaning methods for genome-wide association study
In this study, we investigated the criteria required for the appropriate cleaning of 389 unrelated healthy Japanese samples analyzed using the GeneChip Human Mapping 500K Array Set for GWAS. The samples were randomly subdivided into two groups, and the allele frequencies in the groups were compared for individual SNPs as a quasi-case-control study. Then, observed results were filtered by four parameters (SNP call rate, confidence score obtained using the Bayesian Robust Linear Model with Mahalanobis genotype-calling algorithm, Hardy–Weinberg equilibrium, and minor allele frequency) and assessed for deviation from the nul...
Source: Journal of Human Genetics - October 1, 2008 Category: Genetics & Stem Cells Source Type: research
Genetic imprint of the Mongol: signal from phylogeographic analysis of mitochondrial DNA
AbstractMitochondrial deoxyribonucleic acid (DNA) from 201 unrelated Mongolian individuals in the three different regions was analyzed. The Mongolians took the dominant East Asian-specific haplogroups, and some European-prevalent haplogroups were detected. The East Asians-specific haplogroups distributed from east to west in decreasing frequencies, and the European-specific haplogroups distributed conversely. These genetic data suggest that the Mongolian empire played an important role in the maternal genetic admixture across Mongolians and even Central Asian populations, whereas the Silk Road might have contributed little...
Source: Journal of Human Genetics - September 30, 2008 Category: Genetics & Stem Cells Source Type: research
Mitochondrial DNA variant interactions modify breast cancer risk
AbstractInteractions between mitochondrial deoxyribonucleic acid (mtDNA) variants and the risk of developing breast cancer were investigated using DNA samples collected from non-Jewish European American breast cancer patients and ethnically age-matched female controls. Logistic regression was used to evaluate two-way interactions between 17 mtDNA variants. To control for multiple testing, empiricalP values were calculated using permutation. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to measure the contribution of variants in modifying the risk of developing breast cancer. A highly si...
Source: Journal of Human Genetics - September 30, 2008 Category: Genetics & Stem Cells Source Type: research
Analysis of segregation patterns in Machado –Joseph disease pedigrees
< h3 class= " a-plus-plus " > Abstract < /h3 > < p class= " a-plus-plus " > Machado –Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder of late onset, which is considered the most common form of SCA worldwide. The main goal of this study was to investigate the presence of segregation ratio distortion (SRD) during transmissions of < em class= " a-plus-plus " > ATXN3 < /em > alleles by MJD patients, evaluating the putative role of SRD in the epidemiological representation of the disease. Sixty-two complete sibships, each with one clinically affect...
Source: Journal of Human Genetics - September 30, 2008 Category: Genetics & Stem Cells Source Type: research
Monozygotic female twins discordant for Silver –Russell syndrome and hypomethylation of the H19 -DMR
< h3 class= " a-plus-plus " > Abstract < /h3 > < p class= " a-plus-plus " > Silver –Russell syndrome (SRS) is characterized by growth failure and dysmorphic features, and is frequently caused by hypomethylation of the paternally derived < em class= " a-plus-plus " > H19 < /em > -DMR (epimutation). We observed 5 8/12-year-old female twins discordant for SRS. One twin exhibited SRS-compatible features, such as pre- and postnatal growth failure, relative macrocephaly, triangular face, left hemihypotrophy, and bilateral fifth finger clinodactyly, whereas the other twin showed apparently normal phenotype. Microsatellite analy...
Source: Journal of Human Genetics - September 30, 2008 Category: Genetics & Stem Cells Source Type: research
Comparative study on deletions of the dystrophin gene in three Asian populations
Abstract. The frequency and distribution of deletions of 19 deletion-prone exons clustered in two hot spots in the proximal and central regions of the dystrophin gene were compared in three populations from Singaporean, Japan, and Vietnam. DNA samples obtained from 105 Singaporean, 86 Japanese, and 34 Vietnamese Duchenne muscular dystrophy patients were examined by polymerase chain reaction amplification. Deletions of the examined exons were found in 51.2% of Japanese patients but in 40.0% or less of the Singaporeans and Vietnamese. About two thirds of the deletions were localized in the central region and the remaining de...
Source: Journal of Human Genetics - September 30, 2002 Category: Genetics & Stem Cells Source Type: research
Two families with Wilson disease in which siblings showed different phenotypes
Abstract. We investigated two families with Wilson disease in which siblings showed different clinical phenotypes and different ages at onset. In Family 1, the second and fourth male children demonstrated onset of the neurological type of Wilson disease at 16 and 28 years of age, respectively, and the first female child developed the hepatic type at 38 years of age. In Family 2, the second male child showed neurological symptoms at 32 years of age and was diagnosed as having the hepatoneurological type of Wilson disease; then the 35-year-old first female child was found to have the hepatic type by familial screening. We pe...
Source: Journal of Human Genetics - September 30, 2002 Category: Genetics & Stem Cells Source Type: research
Yfm1, a multicopy marker specific for the Y chromosome and beneficial for forensic, population, genetic, and spermatogenesis-related studies
Abstract. A recently developed microsatellite marker on the Y chromosome, Yfm1, which was originally cloned from a cosmid clone mapped near the DAZ (Deleted in AZoospermia) genes, was used to classify Y chromosomes using an automatic sequencer. Yfm1 could detect multicopies on Y chromosomes in a single polymerase chain reaction, showing four main classes, A, A*, B, and C, according to the number of copies and peak patterns. Compound haplotype analysis of the Y chromosome using the Yfm1 marker with three other biallelic markers on the Y chromosome, SRY, DXYS5Y, and YAP, resulted in nine different haplotypes among different ...
Source: Journal of Human Genetics - September 30, 2002 Category: Genetics & Stem Cells Source Type: research
Single-nucleotide polymorphisms in the class II region of the major histocompatibility complex in Japanese patients with immunoglobulin A nephropathy
Abstract. Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis of unknown etiology and pathogenesis. Immunogenetic studies have not conclusively indicated that human leukocyte antigen (HLA) is involved. As a first step in investigating a possible relationship between HLA class II genes and IgAN, we analyzed the extent of linkage disequilibrium (LD) in this region of chromosome 6p21.3 in a Japanese test population and found extended LD blocks within the class II locus. We designed a case-control association study of single-nucleotide polymorphisms (SNPs) in each of those LD blocks, and determined that...
Source: Journal of Human Genetics - September 30, 2002 Category: Genetics & Stem Cells Source Type: research
Familial 14-Mb deletion at 21q11.2 –q21.3 and variable phenotypic expression
We report a familial case with a proximal interstitial deletion of chromosome 21q [del(21q)]. Although the mother in the family was phenotypically normal, her first child was affected with both sensorineural hearing loss and moderate mental retardation, and the second affected child had mild mental retardation but not sensorineural hearing loss. We determined breakpoints of the del(21q) in the mother and her two affected children by fluorescence in situ hybridization analysis using 45 DNA clones and the molecular analysis using 21 DNA markers. The proximal breakpoint of the del(21q) was located at a region between 0.33 Mb ...
Source: Journal of Human Genetics - September 30, 2002 Category: Genetics & Stem Cells Source Type: research
A girl with 1p36 deletion syndrome and congenital fiber type disproportion myopathy
We report a 4-year-old Japanese girl with 1p36 deletion syndrome whose muscle pathology showed congenital fiber type disproportion (CFTD) myopathy. This is the first case report of 1p36 deletion associated with CFTD. This association may indicate that one of the CFTD loci is located at 1p36.Ski proto-oncogene −/− mice have phenotypes that resemble some of the features observed in patients with 1p36 deletion syndrome. Because fluorescent in situ hybridization analysis revealed that the humanSKI gene is deleted in our patient, some genes in 1p36, includingSKI proto-oncogene, may be involved in muscle hypotonia and delaye...
Source: Journal of Human Genetics - September 30, 2002 Category: Genetics & Stem Cells Source Type: research
