Biomedical subjects

Jun Ohashi

Publications and source records attributed to Jun Ohashi.

At least 37 records · Page 2Linked to original sources

PubMed2004

Comparative study of the haplotype structure and linkage disequilibrium of chromosome 1p36.2 region in the Korean and Japanese populations.

The patterns of linkage disequilibrium (LD) in the human genome provide important information for disease gene mapping. LDs may vary depending on chromosomal regions and populations. We have compared LD and haplotypes defined by SNPs in the chromosome 1p36.2 region of the Korean and Japanese populations. Fifty-eight SNPs in about 418 kb ranging from tumor necrosis factor receptor 2 (TNFR2:TNFRSF1B) to procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) gene were examined in 96 healthy Koreans and Japanese each by direct sequencing and fluorescence correlation spectroscopy combined with the PCR-sequence specific primer method (PCR-SSP-FCS), respectively. Upon pair-wise LD analysis, a total of 25 and 16 out of 58 SNPs greater than MAF 10% were included in LD blocks, encompassing almost 81 kb and 55 kb in total, in Koreans and Japanese, respectively. Both similarities and differences were observed in LD strength and haplotype frequencies between the populations. Considerable similarities were observed in the telomeric region where a long-range block of approximately 80 kb including three genes was found to have strong LDs in both Koreans and Japanese. Significant difference in LD strength was present near the TNFR2 region between the Japanese and Korean populations.

Base Sequence↗

PubMed2004

CD72 polymorphisms associated with alternative splicing modify susceptibility to human systemic lupus erythematosus through epistatic interaction with FCGR2B.

We previously reported association of FCGR2B-Ile232Thr with systemic lupus erythematosus (SLE) in three Asian populations. Because polymorphism of CD72, another inhibitory receptor of B cells, was associated with murine SLE, we identified human CD72 polymorphisms, tested their association with SLE and examined genetic interaction with FCGR2B in the Japanese (160 SLE, 277 controls), Thais (87 SLE, 187 controls) and Caucasians (94 families containing SLE members). Four polymorphisms and six rare variations were detected. The former constituted two major haplotypes that contained one or two repeats of 13 nucleotides in intron 8 (designated as *1 and *2, respectively). Although association with susceptibility to SLE was not detected, the *1 allele was significantly associated with nephritis among the Japanese patients (P=0.024). RT-PCR identified a novel alternatively spliced (AS) transcript that was expressed at the protein level in COS-7 transfectants. The ratio of AS/common isoforms was strikingly increased in individuals with *2/*2 genotype when compared with *1/*1 (P=0.000038) or *1/*2 (P=0.0085) genotypes. Using the two Asian cohorts, significant association of FCGR2B-232Thr/Thr with SLE was observed only in the presence of CD72-*1/*1 genotype (OR 4.63, 95% CI 1.47-14.6, P=0.009 versus FCGR2B-232Ile/Ile plus CD72-*2/*2). Minigene assays demonstrated that the 13-nucleotide repeat and 4 bp deletion within the same haplotype of intron 8 could regulate alternative splicing. The AS isoform lacks exon 8, and is deduced to contain 49 amino acid changes in the membrane-distal portion of the extracellular domain, where considerable amino acid changes are known in CD72(c) allele associated with murine SLE. These results indicated that the presence of CD72-*2 allele decreases risk for human SLE conferred by FCGR2B-232Thr, possibly by increasing the AS isoform of CD72.

Adult↗

PubMed2004

The G/G genotype of a resistin single-nucleotide polymorphism at -420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3.

Insulin resistance is a major cause of type 2 diabetes mellitus (T2DM). Resistin, an adipocyte-secreted hormone, antagonizes insulin. Transgenic mice that overexpress the resistin gene (Retn) in adipose tissue are insulin-resistant, whereas Retn (-/-) mice show lower fasting blood glucose, suggesting that the altered Retn promoter function could cause diabetes. To determine the role of RETN in human T2DM, we analyzed polymorphisms in its 5' flanking region. We found that the -420G/G genotype was associated with T2DM (397 cases and 406 controls) (P=.008; adjusted odds ratio = 1.97 [by logistic regression analysis]) and could accelerate the onset of disease by 4.9 years (P=.006 [by multiple regression analysis]). Meta-analysis of 1,888 cases and 1,648 controls confirmed this association (P=.013). Linkage disequilibrium analysis revealed that the -420G/G genotype itself was a primary variant determining T2DM susceptibility. Functionally, Sp1 and Sp3 transcription factors bound specifically to the susceptible DNA element that included -420G. Overexpression of Sp1 or Sp3 enhanced RETN promoter activity with -420G in Drosophila Schneider line 2 cells that lacked endogenous Sp family members. Consistent with these findings, fasting serum resistin levels were higher in subjects with T2DM who carried the -420G/G genotype. Therefore, the specific recognition of -420G by Sp1/3 increases RETN promoter activity, leading to enhanced serum resistin levels, thereby inducing human T2DM.

Aged↗

PubMed2004

Cardiac function-related gene expression profiles in human atrial myocytes.

To obtain insights into the molecular pathogenesis of heart failure in humans, we have analyzed the expression profiles of>12,000 genes in a total of 17 human specimens of right atrial myocytes. From this large data set, we here tried to identify gene clusters, expression level of which is correlated precisely with clinical parameter values of cardiac function. We could reveal that cardiac myocytes with normal sinus rhythm were clearly differentiated, in the point of view of gene expression, from those with atrial fibrillation. Further, an expression profile-based prediction of arrhythmia by a newly developed "weighted-distance method" could efficiently diagnose our samples. We could even construct calculation formulae for the values of left ventricular ejection fraction based on the expression level of selected genes. To our best knowledge, this is the first report to indicate that pumping ability of heart can be predicted by any measures of atrium.

Adolescent↗

PubMed2004

Association of six polymorphisms of the NOTCH4 gene with schizophrenia in the Japanese population.

The NOTCH4 gene is located at 6p21.3 and involved in the development and patterning of the central nervous systems. Recently, Wei and Hemmings [2000] observed that the gene was associated with schizophrenia. Subsequent to the report, several studies investigated the gene in schizophrenia, with controversial and inconclusive results. In the present study, we investigated six polymorphisms (SNPs 1-5 and a CTG repeat) of the gene in Japanese subjects with schizophrenia (n = 284) and the same number of controls. The polymorphisms include SNP5, which has been observed to be associated with schizophrenia in a Chinese population and two new SNPs 3-4 adjacent to SNP5, in addition to the SNPs 1-2 and the CTG repeat, which were suggested for the association with the disease in the previous study. As a result, no significant difference in genotypic distributions or allelic frequencies of the six polymorphisms of the gene was observed between the patients and the controls. Also, no significant difference was found in frequencies of haplotypes of the six polymorphisms between the patients and the controls. However, the distribution of SNP2 was significantly deviated from Hardy-Weinberg equilibrium in the patients (P = 0.000986), not in the controls, which could be a chance or due to an association of SNP2 with the disease. In conclusion, the present study provided no clear evidence for an association between the NOTCH4 gene and schizophrenia in the Japanese population.

Adult↗

PubMed2004

Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection.

The hemoglobin E variant (HbE; ( beta )26Glu-->Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240-4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection.

Animals↗

PubMed2004

The human histocompatibility leukocyte antigen (HLA) haplotype is associated with the onset of postherpetic neuralgia after herpes zoster.

In some herpes zoster patients, pain persists for more than 3 months or more after healing of vesicular eruptions; this condition is termed postherpetic neuralgia (PHN). We have recently reported the association of the human histocompatibility leukocyte antigens (HLA) haplotype, HLA-A*3303-B*4403-DRB1*1302 with PHN patients; however, it has not been determined whether the haplotype is also associated with herpes zoster that did not develop subsequent PHN. To distinguish whether the haplotype is associated with herpes zoster or the development of PHN, we examined if herpes zoster patients without subsequently PHN are also associated with the HLA haplotype or not. Herpes zoster patients were followed up for more than 6 months, and HLA alleles and haplotypes were compared among the PHN patients (n = 52) the herpes zoster patients who did not develop PHN (n = 42) and healthy controls (n = 125). The frequencies of the risk haplotype in the PHN patients, in the healthy controls and in the herpes zoster patients without subsequent PHN were 16.3, 5.2 and 4.8%, respectively. While the frequency of the risk haplotype was significantly higher in the PHN patients than in the healthy controls (P = 0.0006) no difference was observed between the herpes zoster patients without subsequent PHN and the healthy controls. No significant association was found between the duration of symptoms or the site of herpes zoster and the HLA alleles and the haplotype. These results suggest that the HLA-A*3303-B*4403-DRB1*1302 haplotype plays an important role in the development of PHN after herpes zoster, but not in the onset of herpes zoster.

Adult↗

PubMed2004

Direct determination of MUC5B promoter haplotypes based on the method of single-strand conformation polymorphism and their statistical estimation.

Haplotype-based human genome research is important in identifying disease susceptibility genes efficiently. Although haplotype reconstruction by statistical methods is widely used, direct haplotype determination by molecular techniques has also been developed as a complementary method for statistical estimation. In this study, we demonstrate a molecular haplotyping method making use of single-strand conformation polymorphism (SSCP) gels. We identified 10 common SNPs and a dinucleotide insertion/deletion polymorphism within 2-kb region upstream of the transcription initiation site of MUC5B and determined haplotype structure, dividing the region into two DNA fragments. Real haplotypes were determined unambiguously by our SSCP-based analysis with fragments longer than 1 kb. Haplotypes reconstructed from diploid genotypes in the same region by the statistical methods including EM algorithm were also evaluated. Direct comparison between statistical estimation and direct determination of haplotypes revealed that major haplotypes containing multiple marker sites showing strong LD are estimated in great accuracy but that a variety of haplotypes reflecting weak LD are not reconstructed precisely enough. Our data can be helpful in implementing molecular haplotyping or statistical estimation, since usage of these methods may be determined depending on the haplotype structures.

Base Sequence↗

PubMed2004

Differences in the contribution of HLA-DR and -DQ haplotypes to susceptibility to adult- and childhood-onset type 1 diabetes in Japanese patients.

To clarify heterogeneity in Japanese adult-onset type 1 diabetes, we analyzed the HLA-DR and -DQ haplotypes, depending on the clinical phenotype, and compared them with those in childhood-onset type 1 diabetes (CO). The patients in a previously reported Ehime Study were divided into subgroups by the mode of onset of diabetes: 68 acute-onset type 1 diabetic patients (AO) and 28 slowly progressive type 1 diabetic patients (SO). HLA haplotypes were compared with those of 80 CO patients and 190 control subjects. Two major susceptible HLA haplotypes in the Japanese, DRB1*0405-DQB1*0401 (DR4) and DRB1*0901-DQB1*0303 (DR9), were significantly increased in the AO and CO groups, but only DR9 was increased in the SO group. AO subjects had a higher frequency of DR9 than CO subjects. Accordingly, the DR9:DR4 frequency increased with increasing age of onset. Another susceptible haplotype, DRB1*0802-DQB1*0302 (DR8), was involved only in the CO group. Analysis of haplotype combinations revealed that DR4 and DR9 had significant dosage effects on the AO and CO groups (P < 0.0001), but only DR9 had such an effect in the SO group (P < 0.03). These results suggest differences in the contribution of HLA class II haplotypes to susceptibility of type 1 diabetes depending on the clinical phenotype and also indicate that HLA class II haplotypes may be associated with the onset age of type 1 diabetes.

Adult↗

PubMed2004

[Polymorphism of HLA-DRB1 in Han population in Yunnan and comparison with 9 Han populations].

129 samples of Han population in Yunnan province were detected by polymerase chain reaction and microtitre plate hybridization (PCR-MPH). The samples of DR*15 subgroup being detected by PCR-MPH were further analyzed by Single-Strand Conformation Polymorphism (SSCP). By first polymerase chain reaction and microtitre plate hybridization (PCR-MPH), all of the 129 samples were divided into the following subgroups, viz. DR*01,DR*03,DR*04,DR*0701,DR*08,DR*09012,DR*1001,DR*11,DR*12,DR*13,DR*14,DR*15, DR*1602 and DR*1604. The samples of DR*04, DR*08/12, DR*03/11/13/14 were further detected by second PCR-MPH and the ones of DR*15 by SSCP. 36 kinds of alleles on HLA-DRB1 were detected in these samples. Among them, DRB1*1501(0.1240),DRB1*09012(0.0969), DRB1*08032(0.0930),DRB1*1202(0.0891),DRB1*1201(0.0814), DRB1 *1401(0.0775),DRB1 *0701(0.0620),are the most frequent. The chi(2) test of HLA-DRB1 alleles was done between Yunnan Han and the other 9 Han populations. In detail, comparing with Yunnan Han on the chi(2) test, the chi(2) values of few alleles in the few Han populations was more than 10, they were Xian Han(DR8,chi(2)=13.9712), Shanghai Han(DR4,chi(2)=10.1632), Guangdong Han(DR9,chi(2)=12.6121)and Nanjing Han(DR4,chi(2)=10.5796). Comparing with 9 Han populations, the genetic distance between Yunnan Han and Liaoning Han was the nearest(0.0541),Guangdong Han was the farthest(0.1851). In the 9 Han populations, the genetic distance between Shanghai Han and Nanjing Han was the nearest(0.0122),and the one between Tianjin Han and Shanxi Han was also nearer(0.0219). Based on above analysis, the conclusion may be deduced that the resource of Yunnan Han may be close to Liaoning Han and it was not a typical southern Han population though Yunnan Han are resident in the South. Some gene flow may be exit between Yunnan Han and the local minorities and made Yunnan Han become a special population.

Alleles↗

PubMed2003

Power of association test for detecting minor histocompatibility gene causing graft-versus-host disease following bone marrow transplantation [correction].

Incompatibility of minor histocompatibility antigen (mHa) is a major cause of acute graft-versus-host disease (GVHD) following bone marrow transplantation in human leukocyte antigen (HLA)-matched donor-recipient pairs. To avoid acute GVHD, as many mHa genes as possible need to be identified. In this study, we introduce a comparison of two proportions as an association test for detecting mHa genes in HLA-matched pairs with and without GVHD. Assuming multiple mHa loci, each with two alleles, we evaluated the effects of (1). minor allele frequency of the mHa locus of interest (denoted by p), and (2). probability of GVHD developing in a donor-recipient pair being incompatible at an mHa locus (denoted by r) on the powers of association tests for unrelated pairs and for sib pairs. Our results showed that based on a candidate gene approach, an mHa gene with high p and r values can be detected by the association test with a small sample size. Application of the present method to the Japanese population revealed that the association test for unrelated pairs is more suitable for detecting an mHa gene with a high r value than that for sib pairs. The present method will be helpful to researchers who evaluate the power of association study in advance.

Bone Marrow Transplantation↗

PubMed2003

Power of genome-wide linkage disequilibrium testing by using microsatellite markers.

Linkage disequilibrium (LD) testing is often used in the search for disease genes. In this study, we developed a method for calculating the expected power of genome-wide LD testing by using microsatellite markers under the following assumptions: (1) microsatellite markers have unequally frequent alleles, (2) markers are equally spaced through the human genome, (3) the degree of LD between the disease variant and the marker decays gradually because of recombination and mutation, (4) the population frequency of the disease variant is low (e.g., 0.05), (5) a single-marker test is performed in a case-control study, and (6) the significance level is adjusted by the number of tests to avoid inflation of the type I error. Our calculations revealed a markedly higher power for microsatellite markers than for single nucleotide polymorphism (SNP) markers, even if more SNPs are analyzed, suggesting that the use of microsatellite markers is preferable to the use of SNPs for genome-wide screening under the above assumptions. This method will be helpful to researchers who design genome-wide LD testing with microsatellite markers.

Alleles↗

PubMed2003

Recent divergence of the HLA-DRB104 allelic lineage from the DRB10701 lineage after the separation of the human and chimpanzee species.

Conventional phylogenetic trees for the human leukocyte antigen (HLA)-DRB1 alleles constructed by the neighbor-joining (Saitou and Nei 1987) and UPGMA (Sneath and Sokal 1973) methods using nucleotide sequences of the DRB1 alleles suggest that DRB1*0701 may have diverged from other DRB1 alleles before the separation of the human and chimpanzee species, because of a large number of nucleotide changes in DRB1*0701 compared with any of the other DRB1 alleles. Here we show new evidence that the haplotypes centering on DRB1*0701 and DRB1*04 alleles are the most homologous. This suggests that these haplotypes have derived from the common ancestral haplotype, and that they have likely retained complete linkage disequilibrium even after the divergence of the DRB1*0701 and DRB1*04 allelic lineages. Together with the corresponding haplotype carrying chimpanzee DRB1*0701, which has a high sequence homology to HLA-DRB1*0701, these haplotypes reveal that: (1) the DRB1*04 allelic lineage may have been generated from the DRB1*0701 lineage after the separation of the human and chimpanzee species; (2) the DRB1*04 allelic lineage possibly has a higher substitution rate of DRB1 compared with pseudogene and neutral region; (3) there could be a significant difference in the substitution rate of DRB1 between the DRB1*0701 and DRB1*04 allelic lineages. Based on the difference between the present and previous results, we would like to propose that phylogenetic studies using not only nucleotide sequences of the DRB1 alleles but also haplotypes centering on the alleles should be conducted for understanding detailed phylogenetic relationships of the DRB1 alleles.

Alleles↗

PubMed2003

The absence of evidence for major effects of the frequent SNP +299G>A in the resistin gene on susceptibility to insulin resistance syndrome associated with Japanese type 2 diabetes.

Resistin, specifically secreted from adipocytes, antagonizes insulin and represents a promising candidate gene for type 2 diabetes. We reported that a frequent single nucleotide polymorphism (SNP) +299G>A in this gene is not associated with type 2 diabetes. To determine whether this SNP affects insulin resistance syndrome associated with type 2 diabetes, we examined its effects on susceptibility to obesity, hyperlipidemia and hypertension in type 2 diabetic subjects and on susceptibility to type 2 diabetes by interaction with other frequent genes involved in lipid metabolism, namely, beta3-adrenergic receptor (b3AR) Trp64Arg, phosphodiesterase 3B (PDE3B) c.1389G>A or lysosomal acid lipase (LAL) Thr-6Pro. The 99 type 2 diabetic and 99 control subjects were typed by PCR direct sequencing or PCR-RFLP. No differences in frequencies of obesity, hyperlipidemia and hypertension were found between the type 2 diabetic subjects with G/G and those with G/A or A/A genotypes of the resistin SNP. When the combination of the resistin SNP with each of b3AR, PDE3B and LAL SNPs was assessed, no association with type 2 diabetes was evident. Therefore, the frequent SNP +299G>A in the resistin gene is unlikely to have major effects on susceptibility to insulin resistance syndrome associated with type 2 diabetes in Japanese subjects.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2003

Systematic search for single nucleotide polymorphisms in the 5' flanking region of the human phosphodiesterase 3B gene: absence of evidence for major effects of identified polymorphisms on susceptibility to Japanese type 2 diabetes.

The activation of phosphodiesterase 3B (PDE3B) reduces free fatty acid output from adipocytes. A reduced PDE3B gene expression could lead to insulin resistance. To determine whether there are polymorphisms associated with type 2 diabetes in PDE3B gene promoter, this 5(') flanking region was isolated. The transcription initiation site was located 206bp upstream from the translation start site. Sequences of 2kb of the 5(') flanking region for 24 type 2 diabetic Japanese subjects were initially analyzed using PCR direct sequencing, and the regions including the identified polymorphisms were then examined. In 98 controls and 98 type 2 diabetic subjects, -1947T>C, -567G>A, -465G>T, -458T>C, and -1727_-1726insTCAATT were found. Only -465G>T and this insertion had more than 5% frequencies. Since a complete linkage disequilibrium existed between them, -465G>T was further analyzed, along with a previously identified +1389G>A in the coding region, in a total of 200 controls and 207 type 2 diabetic subjects. These allele frequencies were not significantly different between these two groups (controls vs. cases; -465G>T, 12.0% vs. 10.1%, P=0.435; +1389G>A, 30.3% vs. 33.3%, P=0.408). These genotype distributions were not significantly different between these two groups. The T/T genotype at -465 was rare although this frequency could be higher in type 2 diabetes (4/207 subjects) than controls (0/200 subjects). The linkage disequilibrium existed between -465G>T and +1389G>A, and the estimated haplotype frequencies defined by these SNPs were not significantly different between the cases and controls. Thus, the identified polymorphisms are unlikely to have major effects on susceptibility to Japanese type 2 diabetes.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2003

Systematic search for single nucleotide polymorphisms in the FOXC2 gene: the absence of evidence for the association of three frequent single nucleotide polymorphisms and four common haplotypes with Japanese type 2 diabetes.

FOXC2, a forkhead/winged helix transcription factor, represents a promising candidate gene for type 2 diabetes since transgenic mice that specifically overexpress this gene in adipocytes are lean and insulin sensitive. To determine whether there are single nucleotide polymorphisms (SNPs) in this gene that are associated with type 2 diabetes, sequences of the coding and approximately 1 kb of 5' flanking regions in 24 Japanese type 2 diabetic subjects were initially analyzed using PCR direct sequencing, and the regions containing the identified polymorphisms were then examined. In 200 control subjects, three frequent SNPs were found (g. -512C>T [32.3%] and -350G>T [13.0%] in the 5' flanking region and +1548C>T [10.0%] in the 3' flanking region). Linkage disequilibria were found between all three pairs of these SNPs. Of the eight possible haplotypes defined by these SNPs, only four were found. When the frequencies of these SNPs and the four common haplotypes between 195 type 2 diabetic and 200 control subjects were compared, no association was evident. The +898C>T (Pro300Ser), +907C>A (Leu303Met), 1167_1169delCCA (389delHis), and +1251C>A (Ala417Ala) identified in the coding region were rare, although +907C>A could be higher in type 2 diabetic subjects (1.5%) than in control subjects (0.3%). Thus, the SNPs identified in the FOXC2 gene are unlikely to have major effects on susceptibility to Japanese type 2 diabetes.

Age of Onset↗

PubMed2002

CD36 polymorphism is associated with protection from cerebral malaria.

The human protein CD36 is a major receptor for Plasmodium falciparum-infected erythrocytes and contributes to the pathology of P. falciparum malaria. We performed variation screening of the CD36 gene and examined the possible association between CD36 polymorphisms and the severity of malaria in 475 adult Thai patients with P. falciparum malaria. Accordingly, we identified nine CD36 polymorphisms with a high-frequency (>15%) minor allele. Of these, the frequencies of the -14T-->C allele in the upstream promoter region and the -53G-->T allele in the downstream promoter region were significantly decreased in patients with cerebral malaria compared to those with mild malaria (P=.016 for -14T-->C and P=.050 for -53G-->T). The analysis of linkage disequilibrium (LD) between the nine common polymorphisms revealed that there are two blocks with strong LD in the CD36 gene and that the -14T-->C and -53G-->T polymorphisms are within the upstream block of 35 kb from the upstream promoter to exon 8. Further association testing after the second variation screening in the upstream block indicated that the in3(TG)(12) (i.e., 12 TG repeats in intron 3) allele is most strongly associated with the reduction in the risk of cerebral malaria (odds ratio 0.59; 95% confidence interval 0.40-0.87; P=.0069). We found, by reverse-transcriptase PCR amplification, that in3(TG)(12) is involved in the nonproduction of the variant CD36 transcript that lacks exons 4 and 5. Since exon 5 of the gene is known to encode the ligand-binding domain for P. falciparum-infected erythrocytes, in3(TG)(12) itself or a primary variant on the haplotype with in3(TG)(12) may be responsible for protection from cerebral malaria in Thailand. Results of the present study suggest that LD mapping has potential for detecting a disease-associated variant on the basis of haplotype blocks.

Alleles↗

PubMed2002

Human leukocyte antigen-A specificities and its relation with season of birth in Japanese patients with schizophrenia.

Several studies, including one from Japan, have observed an increase of Human Leukocyte Antigen (HLA)-A24 and A26 in schizophrenia, although others failed to observe the increase. No use of systematic diagnostic criteria and a not-adequately reliable typing technique might have affected the results in the previous studies. We investigated HLA-A specificities in Japanese patients with schizophrenia (DSM-IV), recruited from the same area as in the early Japanese study. A DNA-based technique (polymerase chain reaction-microtiter plate hybridization) was employed. No significant difference was observed in frequencies of any HLA-A specificities between patients and controls, including A24 and A26. No significant association was found between the HLA-A and birth-season in patients. Thus, no evidence was obtained for an association between HLA-A and schizophrenia from the Japanese population.

Adult↗