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Atsuo Taniguchi

Publications and source records attributed to Atsuo Taniguchi.

15 recordsLinked to original sources
PubMed2004

Comparison between various strategies for the disease-gene mapping using linkage disequilibrium analyses: studies on adenine phosphoribosyltransferase deficiency used as an example.

Recently, linkage disequilibrium analyses have been used to detect disease-causing loci based on the common disease-common variant hypothesis. To see what methods can effectively identify the genes, we have to apply them to the practical data obtained from the human population. We extensively performed linkage disequilibrium and haplotype analyses on adenine phosphoribosyltransferase ( APRT) genes in both control and deficient subjects. To examine the power to detect disease-causing loci, we analyzed SNPs, STRPs, and VNTR within and around the APRT gene. When only SNPs were used, P values did not necessarily show significant difference, even at loci close to the mutation site for APRT*J that is exclusively observed among Japanese. However, the examination of the same samples with haplotypes based on the haplotype block data gave sufficient significance. In the case of STRP and VNTR, some single-marker loci showed significant difference. Our study suggested that the use of haplotype analysis based on the haplotype-block structure is more powerful than single-marker locus analysis for the detection of disease-related loci.

Adenine Phosphoribosyltransferase↗
PubMed2004

Familial juvenile hyperuricemic nephropathy: detection of mutations in the uromodulin gene in five Japanese families.

BACKGROUND: Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal-dominant disease characterized by hyperuricemia of underexcretion type, gout, and chronic renal failure. We previously reported linkage on chromosome 16p12 in a large Japanese family designated as family 1 in the present study. Recent reports on the discovery of mutations of the uromodulin (UMOD) gene in families with FJHN encouraged us to screen UMOD mutations in Japanese families with FJHN, including family 1. METHODS: Six unrelated Japanese families with FJHN were examined for mutations of the UMOD gene by direct sequencing. To confirm the results of the mutation screening, parametric linkage analyses were performed using markers in 16p12 region and around other candidate genes of FJHN. RESULTS: Five separate heterozygous mutations (Cys52Trp, Cys135Ser, Cys195Phe, Trp202Ser, and Pro236Leu) were found in five families, including family 1. All mutations were co-segregated with the disease phenotype in all families, except for family 1, in which an individual in the youngest generation was found as a phenocopy by the genetic testing. Revised multipoint linkage analysis showed that the UMOD gene was located in the interval showing logarithm of odds (LOD) score above 6.0. One family carrying no mutation in the UMOD gene showed no linkage to the medullary cystic kidney disease type 1 (MCKD1) locus, the genes of hepatocyte nuclear factor-1beta (HNF-1beta), or urate transporters URAT1 and hUAT. CONCLUSION: Our results gave an evidence for the mutation of the UMOD gene in the majority of Japanese families with FJHN. Genetic heterogeneity of FJHN was also confirmed. Genetic testing is necessary for definite diagnosis in some cases especially in the young generation.

Amino Acid Sequence↗
PubMed2003

Validation of a Japanese version of the Stanford Health Assessment Questionnaire in 3,763 patients with rheumatoid arthritis.

OBJECTIVE: To develop and validate a self-administered instrument for measuring functional status in Japanese-speaking rheumatoid arthritis patients. METHODS: We translated the Stanford Health Assessment Questionnaire (HAQ) into Japanese (original HAQ), and then made a tentative Japanese version of the HAQ (J-HAQ) with culturally appropriate modifications of the arising, eating, and reach category questions. The questionnaire was then administered to 3,763 RA patients (82.6% female; mean age 58.0 years; mean onset age 47.4 years; mean disease duration 10.5 years). RESULTS: This instrument showed excellent internal reliability (Cronbach's alpha = 0.927), with a mean interitem correlation of 0.60. For the arising category question, the J-HAQ asks about arising from a futon in addition to a bed because futons are still common in Japanese culture. Arising from a futon is generally more difficult for disabled individuals than is arising from a bed, so the arising score was higher in the J-HAQ (mean score 0.82) than in the original HAQ (0.48). The average scores for the eating and reach categories were virtually identical for the original HAQ and the J-HAQ, with correlation coefficients of 0.979 and 0.926, respectively. Thus, the overall disability index (average of the scores for all functional areas) was higher in the J-HAQ (0.81) than in the original HAQ (0.76), although the correlation coefficient was high (0.993). The test-retest reliability value (0.92), studied at a 1-week interval, revealed identical disability index scores measured on the 2 occasions. CONCLUSION: The final version of the J-HAQ is a valid and reliable instrument for measuring functional status in Japanese-speaking RA patients.

Activities of Daily Living↗
PubMed2002

Polymorphisms in the methylenetetrahydrofolate reductase gene were associated with both the efficacy and the toxicity of methotrexate used for the treatment of rheumatoid arthritis, as evidenced by single locus and haplotype analyses.

5,10-Methylenetetrahydrofolate reductase (MTHFR), a key enzyme involved in folate metabolism, has two common polymorphisms that affect enzyme activity. The objective of this study was to examine whether there was a correlation between the genotype or haplotype of the MTHFR gene and the efficacy or toxicity of methotrexate (MTX) in the treatment of rheumatoid arthritis. MTX-treated rheumatoid arthritis patients (n = 106) were selected from outpatient clinics and used for a retrospective study to examine the correlation between genotypes or haplotypes concerning polymorphisms of the MTHFR gene, and the efficacy or toxicity of MTX. Estimation of the haplotype frequencies was performed by maximum likelihood estimation based on expectation maximization algorithm. Single locus analysis examining each locus separately showed that patients with 1298C were receiving significantly lower doses of MTX compared to patients without [P < 0.05, relative risk (RR) = 2.18, 95% confidence interval (CI) 1.17-4.06], while a higher rate of overall MTX toxicity was observed in patients with 677T than those without (P < 0.05, RR = 1.25, 95% CI 1.05-1.49). An estimation of haplotype frequencies showed that there was no 677T-1298C haplotype in the population. Posterior distribution of the diplotype configuration for each individual was concentrated on a single configuration. Patients with the 677C-1298C haplotype were receiving lower doses of MTX than those without (P < 0.05, RR = 2.14, 95% CI 1.13-4.07), while subjects with 677T-1298A had a higher frequency of side-effects from MTX (P < 0.05, RR = 1.42, 95% CI 1.11-1.82). Both single locus and haplotype analyses suggest that polymorphisms within the MTHFR gene are associated with both the efficacy and toxicity of MTX in rheumatoid arthritis patients. Pharmacokinetic studies are necessary to prove the association.

Antirheumatic Agents↗
PubMed2002

Comparison of the Rau method and the Larsen method in the evaluation of radiographic progression in early rheumatoid arthritis.

OBJECTIVE: To investigate the usefulness of the radiographic scoring method proposed by Rau, et al for evaluation of joint damage in patients with early rheumatoid arthritis (RA). METHODS: Radiographs of hands and feet of 30 prospectively observed patients with early RA were assessed by the Rau method, the Larsen method, and count of erosive joints. The standardized response mean (SRM) was used to estimate the sensitivity to change of each method of assessment. RESULTS: Although the Rau method evaluates only the amount of bony erosion, nearly equivalent radiographic progression was observed with the Rau and the Larsen methods. Radiographic changes in the first year were sensitively identified by all 3 methods (SRM for Rau method 0.83, Larsen method 0.88, and count of erosive joints 0.84). However, in the period from 2 to 6 years after entry into the study, sensitivity to change was maintained with use of the Rau (SRM 1.38) and Larsen (SRM 0.95) methods, but not by count of erosive joints (SRM 0.49). While an apparent ceiling effect was observed after 2 years in count of erosive joints, no ceiling effects were noted for the Rau and Larsen methods. CONCLUSION: Our study showed that the usefulness of the Rau method is equivalent to the Larsen method in clinical assessment of radiographic progression in early RA.

Arthritis, Rheumatoid↗
PubMed2002

The inflammatory process in the mechanism of decreased serum uric acid concentrations during acute gouty arthritis.

OBJECTIVE: To clarify the mechanism of decreased serum uric acid (SUA) concentrations during acute gouty arthritis. METHODS: Data from patients with acute gouty arthritis during and after an attack were investigated retrospectively. Other investigations, including changes in urinary excretion and biochemical markers, were performed prospectively. RESULTS: SUA was significantly lower in the acute phase (7.5 +/- 1.4 mg/dl) than in the intercritical phase (8.5 +/- 0.9 mg/dl) (p < 0.0001). During the acute gout phase, a normal SUA level was found in 20 of 41 patients (49%). C-reactive protein (CRP) during acute attacks was significantly correlated with plasma interleukin 6 (IL-6) and cortisol (r = 0.645, p < 0.005; r = 0.460, p < 0.05). Percentage change in SUA at onset of attack correlated with CRP and IL-6 (r = 0.762, p < 0.0001; r = 0.630, p < 0.005), as well as with increased urinary excretion of uric acid, estimated by percentage change in fractional excretion of uric acid (FEua) during attack (r = 0.447, p < 0.05). Further, change in FEua was correlated with plasma cortisol levels during the acute attack (r = 0.534, p < 0.05). CONCLUSION: Decrease in SUA during acute gouty arthritis is associated with increased urinary excretion of uric acid; an inflammatory process may play a role in the mechanism.

Acute Disease↗
PubMed2002

Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene.

OBJECTIVE: N-acetyltransferase 2 (NAT2) is a key enzyme for the acetylation of sulfasalazine (SSZ). We examine whether there was a correlation between diplotype configurations (combinations of 2 haplotypes for a subject) at the NAT2 gene and the adverse effects of SSZ used for the treatment of rheumatoid arthritis (RA). METHODS: The findings from 144 patients with RA who had been treated with SSZ were collected from our outpatient department and used for a retrospective study. Haplotype analysis was performed by the maximum-likelihood estimation based on the EM algorithm using the obtained polymorphism data. RESULTS: Sixteen patients (11.1%) had experienced adverse effects from SSZ, the most common being allergic reactions including rash and fever. The slow acetylators who had no NAT2*4 haplotype had experienced adverse effects more frequently (62.5%) than the fast acetylators who had at least one NAT2*4 haplotype (8.1%) (p < 0.001, OR 7.73, 95% CI 3.54-16.86). In 25% of the slow acetylators, the adverse effects were so severe that they were hospitalized. CONCLUSION: Genotyping the NAT2 gene followed by estimation of diplotype configuration before administration of SSZ is likely to reduce the frequency of adverse effects in Japanese patients with RA.

Acetylation↗
PubMed2002

[Pharmacogenetics of disease modifying anti-rheumatic drugs].

There are large differences in the effectiveness of disease modifying anti-rheumatic drugs(DMARD) from one person to the next. Adverse drug reactions caused by DMARD can also occur to some patients, but do not occur to others. One possible cause of the differences in the effectiveness and adverse drug reactions is genetic variation in how individuals metabolize drugs. The Human Genome Project heralds new opportunities for using information about genetic variation to predict responses to drug therapies, called pharmacogenetics. Based on pharmacogenetics, tailor-made drug therapy is going to be realized. Our recent studies revealed the relationship between genetic polymorphisms of drug metabolizing enzymes and the efficacy of methotrexate or sulfasalazine in patients with rheumatoid arthritis, suggesting pharmacogenetics is applicable to the treatment of rheumatoid arthritis.

Antirheumatic Agents↗