Disease In Asian Population Research Articles

Sa1051 Validation of Fatty Liver Index and Lipid Accumulation Product for Identifying Nonalcoholic Fatty Liver Disease in Asian Population With Metabolic Syndrome

Sa1051 Validation of Fatty Liver Index and Lipid Accumulation Product for Identifying Nonalcoholic Fatty Liver Disease in Asian Population With Metabolic Syndrome

A meta-analysis about the relation of polymorphism at the sites + 49 of cytotoxic T-lymphocyte associated antigen 4 gene with the susceptibility of Graves' disease in Asian population

Objective To review the quantitative relationship of polymorphism at the sites +49 of cytotoxic T-lymphocyte associated antigen 4 gene with the susceptibility of Graves' disease(GD) in Asian population.Methods The Medline,PubMed,Embase,Web of Science,and Chinese Biomedical Literature Database on disc (CBM disc) databases were searched and used in meta-analysis to analyze the data in the articles collected.Results This analysis included a total of 24 papers,and GD patients and healthy population control group were composed of 4 832 cases and 5 643 subjects respectively.This paper revealed that in the general population,the Chinese people and the Japanese crowd,all the genetic models (allele,co-dominant model,dominant model,recessive model) were statistically significant,indicating that CTLA-4 +49 A allele could reduce the risk of GD.Conclusions The CTLA-4 +49 G→A mutation allele may serve as a factor in reducing the risk of GD susceptibility in Asian population. Key words: Graves' disease; Cytotoxic T-lymphocyte associated antigen 4 gene; Polymorphisms; meta-analysis

Meta-analysis of Genetic Polymorphisms and Ophthalmologic Disease Risk in Asian Populations: a Case of DNA Repair XRCC1 Gene

This study aimed to assess a meta-analysis of the association of XRCC1 polymorphisms with the risk of various ophthalmologic diseases in Asian population. This meta-analysis was performed by critically reviewing reveals 38 studies involving 1373 cases and 1745 controls. Among all the eligible studies, one focused on Arg194Trp polymorphism, nine described the Arg399Gln and no article investigated on Arg280His. There was a large between-study heterogeneity in ORs of individual studies of the dominant model (chi2 = 74.18, I2 = 58.9%, p = 0.013) and the additive (chi2 = 56.18, I2 = 41.4%, p = 0.091) models, but a moderate heterogeneity in the recessive model (chi2 = 72.27, I2 = 78.8%, p = 0.000) was observed. So, we pooled the results using the random-effect analysis and found that Arg399Gln has a weak relation with ophthalmologic disease in the recessive (OR = 0.96, 95% CI: 0.64-1.44), the dominant (OR = 1.05, 95% CI: 0.82-1.33) and the additive (OR = 1.15, 95% CI: 0.77-1.70) and models. The present meta-analysis correspondingly shows that comprising diverse population is very important since susceptibility loci might vary indifferent ethnic groups. To ratify our findings, widespread studies with enlarged sample size and various populations are essential to explain the role of all polymorphism of XRCC1 genes in the pathogenesis of ophthalmologic diseases. Finally, our meta-analysis showed Arg399Gln variant was not associated with increased ophthalmologic diseases risk via dominant and recessive modes among Asian population.

Association between HLA-B*46 Allele and Graves Disease in Asian Populations: A Meta-Analysis

Graves' disease (GD) is a leading cause of hyperthyroidism, which affects 1.0-1.6% of the general population. Previous studies reported a higher GD prevalence in Asian populations compared to Caucasian populations. The etiology of GD involves complex interactions between predisposing genes and environmental triggers. Genetic studies have shown that the human leukocyte antigen (HLA) is an important candidate genetic region associated with GD in Asian populations. However, the results were inconsistent and inconclusive. Here, we performed a meta-analysis to evaluate the role of the HLA-B*46 allele in GD in Asian populations. A total of 14 case-controlled studies on the association of the HLA-B*46 allele in 1743 GD patients and 5689 controls were included. Our results showed a trend toward an increased risk of GD in HLA-B*46-positive subjects compared to those HLA-B*46-negative (OR = 2.48; 95% CI = 1.96-3.13, P < 0.01). However, there were some limitations to the current meta-analysis, such as heterogeneity (Pheterogeneity < 0.01 and I2 = 68.0%) or the different typing methods (serological and genotyping methods). The meta-analysis indicated that the HLA-B*46 allele is a risk factor for GD in Asian populations. Future studies on the role of the HLA-B*46 allele in GD should consider complications such as periodic paralysis, ophthalmopathy and recurrence.

Abstract PR8: Beta-diversity metrics of the upper digestive tract microbiome are associated with body mass index.

Abstract Recent studies implicate the gut microbiome in the etiology of obesity. However, the contribution of the microbiome remains uncertain due to conflicting results. Previous studies have examined different populations and ages, but most have focused on the fecal microbiome, while few studies have examined the role of microbial diversity at other body sites. To explore the association between obesity and the microbial diversity of the upper digestive tract, we studied in cross-section a cohort of 659 healthy Chinese adults (ages 34 to 67 years) with a measured body mass index range of 15.0 to 35.7. We characterized the upper gastrointestinal tract microbiome using the HOMIM DNA microarray, which tests for the presence of approximately 300 species/strains of bacteria. We characterized alpha-diversity using taxa counts, and we created beta-diversity metrics using an unweighted unifrac distance matrix of pairwise comparisons of the whole cohort. We performed unsupervised clustering in this matrix and found support for three clusters, and we generated principal coordinate vectors from the matrix. Body mass index was examined as a continuous variable on the log scale in regression models adjusted for age, sex, tobacco smoking, alcohol drinking, antibiotic use, sample collection device, and the number of decayed, missing, and filled teeth. We found that alpha-diversity (numbers of strains, species, genera, families, orders, classes, or phyla) was not associated with body mass index. The presence or absence of each individual species/strain of bacteria on the HOMIM DNA microarray was not associated with body mass index after Bonferroni correction for multiple comparisons. However, beta-diversity, as assessed by cluster membership (first cluster compared with third cluster, p=0.0121; second cluster compared with third cluster, p=0.0002) and principal coordinate vectors, scaled to their interquartile ranges (p-values for the third and fourth vectors were p=0.0132 and p=0.0280, respectively), were associated with body mass index. Moreover, in adjusted models with multiple microbial diversity metrics, cluster membership remained independently associated with body mass index, while the vector associations were attenuated. Individuals in the first (median body mass index 22.35, interquartile range 19.17-23.31) and second (median body mass index 22.55, interquartile range 20.50-24.38) clusters had lower median body mass indexes that fall within the optimum Asian BMI range than the median body mass index in the third cluster (23.59, interquartile range 21.50-25.32), which is considered to fall in the range of increased risk for obesity-related diseases in Asian populations. Our results demonstrate for the first time that beta-diversity in the upper digestive tract microbiome is associated with body mass index. Future longitudinal, prospective studies should address whether the upper digestive tract microbiome plays a causal role for obesity. This proffered talk is also presented as Poster 56. Citation Format: Shih-Wen Lin, Neal D. Freedman, Jianxin Shi, Mitchell H. Gail, Guoqin Yu, Vanja Klepac-Ceraj, Bruce J. Paster, Bruce A. Dye, Wen-Qiang Wei, Jin-Hu Fan, You-Lin Qiao, Sanford M. Dawsey, Christian C. Abnet. Beta-diversity metrics of the upper digestive tract microbiome are associated with body mass index. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr PR8.

Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population

BackgroundPreliminary evidence has suggested the role of inflammation in development and prognosis of cardiovascular diseases and cancers. Most of the prognostic studies failed to account for the effects of co-morbid conditions as these might have raised the systemic inflammation. We used neutrophil lymphocyte ratio (NLR) as a measure of systemic inflammation and investigated its association with prevalent chronic conditions.MethodsPresent study is a cross sectional study conducted on population of Karachi, Pakistan. A detailed questionnaire about the demographic details of all subjects was filled and an informed consent obtained for blood sampling. Multinomial regression analyses were carried out to investigate the relationship between NLR and prevalent chronic conditions.Results1070 apparently healthy individuals participated in the study. Proportion of individuals with hypertension was higher in middle and highest tertile of NLR as compared to the lowest tertile (18.2% & 16.1% compared to 11.8%). Individuals with hypertension were 43% (RRR = 1.43, 95% CI 0.94-2.20) and 66% (RRR = 1.69, 95% CI 1.09-2.54) more likely to be in the middle and highest tertile of NLR respectively compared to the baseline group. Similarly, individuals with diabetes mellitus were 53% (RRR = 1.53, 95% CI 0.93-2.51) and 65% (RRR = 1.65, 95% CI 1.01-2.71) more likely to be in the middle or highest tertile of NLR as compared to the baseline NLR group.ConclusionsSystemic inflammation measured by NLR has a significant association with prevalent chronic conditions. Future research is needed to investigate this relationship with longitudinal data to establish the temporal association between these variables.

Improved assay for differential diagnosis between Pompe disease and acid α-glucosidase pseudodeficiency on dried blood spots

The high frequency (3.3–3.9%) of acid α-glucosidase pseudodeficiency, c.[1726G > A; 2065G > A] homozygote (AA homozygote), in Asian populations complicates newborn screening for Pompe disease (glycogen storage disease type II or acid maltase deficiency) on dried blood spots, since AA homozygotes have a considerably low enzyme activity. We observed that hemoglobin in the enzyme reaction solution strongly interferes with the fluorescence of 4-methylumbelliferone released from 4-methylumbelliferyl α- d-glucopyranoside (4MU-αGlc) by acid α-glucosidase. Therefore, we have searched for a method to effectively eliminate hemoglobin in the reaction solution. Hemoglobin precipitation with barium hydroxide and zinc sulfate (Ba/Zn method) carried out after the enzyme reaction considerably enhances the fluorescence intensity while it does not reduce the intensity to any extent as can occur with conventional deproteinization agents like trichloroacetic acid. The Ba/Zn method greatly improved the separation between 18 Japanese patients with Pompe disease and 70 unaffected AA homozygotes in a population of Japanese newborns in the assay with 4MU-αGlc on dried blood spots. No overlap was observed between both groups. We further examined acid α-glucosidase activity in fibroblasts from 11 Japanese patients and 57 Japanese unaffected individuals including 31 c.[1726G; 2065G] homozygotes, 18 c.[1726G; 2065G]/[1726A; 2065A] heterozygotes and 8 AA homozygotes to confirm that fibroblasts can be used for definitive diagnosis. The patients were reliably distinguished from three control groups. These data provide advanced information for the development of a simple and reliable newborn screening program with dried blood spots for Pompe disease in Asian populations.

Clinical Characteristics of Kidney Disease in Japanese HIV-Infected Patients

Background: Kidney disease has become an important cause of morbidity and mortality in HIV-infected patients in Western countries. Japan is a country with an increasing number of newly infected HIV patients. However, only a few studies have investigated kidney disease in Asian populations infected with HIV. Methods: We studied the prevalence of kidney disease by reviewing the clinical data of 732 HIV-infected Japanese patients. Risk factors for proteinuria, albuminuria, and renal dysfunction were determined using multivariate logistic regression analysis. Results: Microalbuminuria, macroalbuminuria and proteinuria were present in 13.2, 4.55 and 9.52% of patients, respectively. The prevalence of chronic kidney disease of any stage and CKD ≧ stage 3 was 15.4 and 9.70%, respectively. Multivariate analysis showed significant associations between increasing levels of serum creatinine and cholesterol, and the coexistence of diabetes, hypertension and hepatitis C coinfection with either proteinuria or albuminuria, which was significantly related to the presence of renal dysfunction. Lower CD4 cell count was associated with the presence of renal dysfunction, but higher HIV-RNA level was not. Conclusions: Our study has shown the international dimension of the burden of kidney disease in HIV-infected patients. Either proteinuria or albuminuria is likely the most significant factor for renal dysfunction in these patients.

Association of SUMO4 M55V polymorphism with susceptibility to autoimmune and inflammatory diseases: a meta‐analysis

The purpose of this study was to generate large-scale evidence on whether SUMO4 M55V polymorphism is associated with autoimmune and inflammatory diseases using a meta-analysis. We surveyed studies on the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases in PubMed. Meta-analysis was performed for genotypes AG versus AA, GG versus AA, GG versus AA + AG, AG + GG versus AA and G allele versus A allele in a fixed/random effect model. We identified 16 studies (11, 407 cases and 10, 679 controls) using PubMed search. When all groups were pooled, we detected the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases (G versus A: OR = 1.11, 95%CI = 1.03-1.19, P = 0.005; AG +GG versus AA: OR=1.17, 95%CI=1.06-1.28, P=0.001; GG versus AA+AG: OR=1.07, 95%CI=0.94-1.21, P=0.29; GG versus AA: OR=1.15, 95%CI=1.00-1.34, P=0.06; AG versus AA: OR=1.15, 95%CI=1.08-1.23, P<0.0001). In subgroup analyses, we detected the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases in Asian population (G versus A: OR=1.18, 95%CI=1.08-1.28, P=0.0001; AG+GG versus AA: OR=1.30, 95%CI=1.16-1.45, P<0.00001; GG versus AA+AG: OR=1.04, 95%CI=0.78-1.37, P=0.80; GG versus AA: OR=1.20, 95%CI=0.99-1.45, P=0.07; AG versus AA: OR=1.32, 95%CI=1.18-1.49, P<0.00001). But the association was not found in Caucasian population. Meanwhile, an association of SUMO4 M55V polymorphism with autoimmune diabetes was found (G versus A: OR=1.18, 95%CI=1.08-1.30, P=0.0005; AG+GG versus AA: OR=1.22, 95%CI=1.13-1.32, P<0.00001; GG versus AA+AG: OR=1.15, 95%CI=0.96-1.38, P=0.13; GG versus AA: OR=1.32, 95%CI=1.08-1.60, P=0.006; AG versus AA: OR=1.23, 95%CI=1.13-1.33, P<0.00001). This meta-analysis demonstrates the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases, especially in Asian population.

Genomic copy number variations in three Southeast Asian populations

Research on the role of copy number variations (CNVs) in the genetic risk of diseases in Asian populations has been hampered by a relative lack of reference CNV maps for Asian populations outside the East Asians. In this article, we report the population characteristics of CNVs in Chinese, Malay, and Asian Indian populations in Singapore. Using the Illumina Human 1M Beadchip array, we identify 1,174 CNV loci in these populations that corroborated with findings when the same samples were typed on the Affymetrix 6.0 platform. We identify 441 novel loci not previously reported in the Database of Genomic Variations (DGV). We observe a considerable number of loci that span all three populations and were previously unreported, as well as population-specific loci that are quite common in the respective populations. From this we observe the distribution of CNVs in the Asian Indian population to be considerably different from the Chinese and Malay populations. About half of the deletion loci and three-quarters of duplication loci overlap UCSC genes. Tens of loci show population differentiation and overlap with genes previously known to be associated with genetic risk of diseases. One of these loci is the CYP2A6 deletion, previously linked to reduced susceptibility to lung cancer.

Diabetes and 15-year Cardiovascular Mortality in a Chinese Population: Differential Impact of Hypertension and Metabolic Syndrome

It remains unclear if the risk for cardiovascular (CV) mortality in patients with diabetes mellitus (DM) is equivalent to that in patients with a history of cardiac disease in Asian populations. The aims of the present study were to investigate whether or not non-heart disease (HD) DM subjects have a similar risk of CV mortality as HD patients without DM (non-DM HD), and whether or not hypertension (HT) or metabolic syndrome (MS) is a CV mortality marker for diabetic subjects identified from a community-based population. We followed 11,058 Chinese people aged > or = 30 years on Kinmen island for a median of 15.0 years. The age-, sex- and smoking-adjusted hazard ratios for CV mortality were 3.56 [95% confidence interval (CI): 1.99-6.36] for DM subjects with HD, 1.64 (95% CI: 1.25-2.16) for DM without HD (non-HD DM) subjects, and 1.63 (95% CI: 1.09-2.44) for non-DM HD patients, when compared with subjects without DM and HD. Among the 827 non-HD DM subjects identified at the baseline survey, the age-, sex- and smoking-adjusted hazard ratios for CV mortality were 2.36 (95% CI: 1.30-4.28) for the presence versus absence of HT, and 1.23 (95% CI: 0.65-2.34) for the presence versus absence of MS. Non-HD DM subjects had a similar risk of CV mortality to non-DM HD subjects in this Chinese population. The presence of HT but not MS substantially increased CV mortality risk in the DM subjects.

Changing Epidemiology and Future Challenges of Inflammatory Bowel Disease in Asia

In the past decade, many countries in Asia, in particularly in East Asia, are experiencing a progressive rise in the incidence and prevalence of inflammatory bowel disease (IBD). Improved physician awareness and diagnostic methods are unlikely to fully account for this rapid increase. This epidemiological shift is likely to relate to industralization, westernization of lifestyles and changes in eating habits, as part of the socioeconomic development in Asia, although many of these putative environmental factors have not been formally investigated in Asian cohorts. Genetic factors for IBD differ between Asia and the West. NOD2/CARD15 mutation, repeatedly observed in the Caucasian populations, is not associated with Crohn’s disease in Asian populations. Familial clustering is generally uncommon in Asia but it is expected to increase as the IBD prevalence in this region rises. Ethnic-racial differences of IBD have been described and Indians appear to be most affected in South-East Asia. Clinical manifestation of IBD in Asia resemble the Western population in general, but with some differences, including higher prevalence of males and ileocolonic disease, lower disease severity, surgical rates and extraintestinal manifestations. These differences may relate to time factor, genetic background and environmental factors. This review summarises recent epidemiological data of IBD including environmental factors associated with the development of IBD in Asia. Future research focusing on studying the epidemiology of IBD in an area of rapidly increasing prevalence such as Asia will allow the opportunity to identify potential risk factors and provide a better understanding of the aetiology of disease in the Asian population. (Intest Res 2010;8:1-8) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

The CKD-EPI Equation and MDRD Study Equation Find Similar Prevalence of Chronic Kidney Disease in Asian Populations

Letters15 December 2009The CKD-EPI Equation and MDRD Study Equation Find Similar Prevalence of Chronic Kidney Disease in Asian PopulationsCharumathi Sabanayagam, MD, MMed, Tien Y. Wong, MD, PhD, and E. Shyong Tai, MBChBCharumathi Sabanayagam, MD, MMedFrom Singapore Eye Research Institute, National Institute of Singapore, Singapore, 168751, Singapore.Search for more papers by this author, Tien Y. Wong, MD, PhDFrom Singapore Eye Research Institute, National Institute of Singapore, Singapore, 168751, Singapore.Search for more papers by this author, and E. Shyong Tai, MBChBFrom Singapore Eye Research Institute, National Institute of Singapore, Singapore, 168751, Singapore.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-151-12-200912150-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Levey and colleagues (1) presented a new equation for estimating glomerular filtration rate (GFR), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and compared the prevalence of chronic kidney disease (CKD) in the U.S. population estimated by the new equation with the prevalence estimated by the MDRD (Modification of Diet in Renal Disease) Study equation. The authors reported that the new CKD-EPI equation gives a lower estimated prevalence of CKD than the MDRD Study equation and suggested testing this new equation in other ethnic groups. Recent studies in Asian populations show that the epidemiologic pattern and the relative ...

The CKD-EPI Equation and MDRD Study Equation Find Similar Prevalence of Chronic Kidney Disease in Asian Populations

Letters15 December 2009The CKD-EPI Equation and MDRD Study Equation Find Similar Prevalence of Chronic Kidney Disease in Asian PopulationsAndrew S. Levey, MD, Lesley A. Stevens, MD, MS, and Josef Coresh, MD, PhDAndrew S. Levey, MDFrom Tufts Medical Center, Boston, MA 02111; and Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.Search for more papers by this author, Lesley A. Stevens, MD, MSFrom Tufts Medical Center, Boston, MA 02111; and Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.Search for more papers by this author, and Josef Coresh, MD, PhDFrom Tufts Medical Center, Boston, MA 02111; and Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-151-12-200912150-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Sabanayagam and colleagues report that mean estimated GFR when computed with the CKD-EPI equation is higher than with the MDRD Study equation in a young Asian sample (presumably with high GFR) of mixed ethnicity. This confirms our findings in a predominantly U.S. and European sample and is expected because of the form and coefficients for the variables for both equations. Studies with measured GFR must evaluate the accuracy of GFR estimates in Asian persons. The CKD-EPI equation has no “Asian coefficient,” so we suspect that it will not be as accurate in Asian persons as in our ...

Identification of the SBDS Gene Mutation in Japanese Patients with Bone Marrow Failure Syndrome

Shwachman-Diamond syndrome (SDS) which is caused by mutations in both alleles of the SBDS gene, is an inherited bone marrow failure syndrome (BMFS) typified by pancreatic exocrine insufficiency, skeletal defects, and an elevated risk for developing hematologic malignancy. The functional consequences of SBDS mutation have not yet been characterized, although short telomeres of leukocytes have been observed in affected patients. About one third of patients with aplastic anemia (AA) show significant reductions in telomere length. Several groups, including our own, have recently reported that some of the patients of acquired AA or myelodysplasia (MDS) with telomere shortening may be explained by mutations of the telomerase complex genes. However the responsible genes have not yet been identified in most of the patients of BMFS with telomere shortening. A recent study showed a heterozygous mutation of SBDS, 258+2T>C, in 4 out of 91 patients with apparently acquired AA (Blood . 2007; 110: 1141). Therefore, we carried out an investigation to determine whether mutations in SBDS are associated with the disease in our cohort of Japanese BMFS patients. We analyzed mutation of SBDS gene among 110 BMFS patients with acquired AA (n=38) or with MDS (RA) (n=72) diagnosed between 1993 to 2005 at the Nippon Medical School. We identified the 258+2 T>C mutation at intron 2 in an AA patient only, which was absent in 200 controls. This mutation found in SDS patients, is thought to disrupt the donor splice site in intron 2, engaging a cryptic upstream splice site at positions 251 to 252 and leading to protein truncation at codon 84 by frameshift. Previous study reported that the 4 AA patients with heterozygous for SBDS 258+2T>C mutation were younger than other AA patients without mutation (Blood . 2007; 110: 1141). However our patient with the mutation was a 64 yr-old female. She was clinically diagnosed with mild AA, and the medical history, family history, and the physical examination were not suggestive of an inherited disease. We observed this patient without treatment, because her hematological data was not severe, and blood transfusion was not necessary for her. Our study sowed that she was not found to have TERC and TERT mutation. These sequence polymorphisms were identified in both intronic and exonic regions of the gene. IVS2-70T/C, IVS2-71G/A, and 141C>T were identified at similar allele frequencies in patients and controls. Calado et al showed 201A>G in 13 out of 91 patients and 38 out of 276 controls (Blood . 2007; 110: 1141). However, we didn't identify 201A>G among our patients, as observed by previous Japanese population studies (Haematologica . 2007; 92: 1573). The incidence of 201A>G is much lower in Japanese population compared with that in western countries. Subsequently, we compared the length of telomeres of mononuclear cells using southern blot in the AA patient with heterozygous for SBDS 258+2T>C mutation with age-much controls. The AA patient with heterozygous for SBDS 258+2T>C mutation didn't show shorter telomere than age-much controls. In patients with acquired AA heterozygous for SBDS mutation, it was reported that granulocytes' telomeres were short via a telomerase-independent pathway, but lymphocytes' telomeres were in the normal range. Since this is an archival case, we could not examine the length of telomere of each leukocyte subsets from this patient. We speculated the reason of this patient not showing shorting telomere that lymphocytes were dominant in MNC of this patient's peripheral blood. Finally, our data presented here are consistent with the idea that SBDS mutation contributes to the pathogenesis of a subset of BMFS in a subset of these patients. The largest controlled epidemiologic studies reported that the incidence of AA in the Western countries is 2 per million per year comparing the 2- to 3-fold higher rate in Asia. However, our and another study (Haematologica . 2007; 92: 1573) showed that the mutational frequencies of SBDS gene among Japanese BMFS patients were lower than that for other ethnic groups and that this genetic difference could not explain the higher incidence of the disease in Asian populations.

Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol and the incidence of cardiovascular disease in an urban Japanese cohort study: The Suita study

Objective Only a small number of population-based cohort studies have directly compared the predictive value of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDLC) for coronary artery disease in Asian populations, such as Japan. Methods We performed an 11.9-year cohort study of 4694 men and women, aged 30–74 years, selected randomly from an urban general population in Japan. Baseline LDL-C levels were estimated using the Friedewald formula. The predictive values of LDL-C and non-HDLC for myocardial infarction (MI) and stroke were compared. Results and conclusion During the follow-up period, there were 80 incident cases of MI and 139 of stoke, comprised of 23 intracerebral hemorrhages, 85 cerebral infarctions and 31 other types of stroke. The Hazard ratio (HR) for MI was highest in the top quintile of LDL-C (HR: 3.03, 95% CI, 1.32–6.96) when male and female data were combined. The HR for MI was also highest in the top quintile of non-HDLC (HR: 2.97, 95% CI, 1.26–6.97). Analysis of trends showed a significant positive relationship between MI incidence and serum LDL-C and non-HDLC levels (both P = 0.02). However, there was no relationship between the incidence of any subtype of stroke and either LDL-C or non-HDLC. The predictive value of LDL-C and non-HDLC for MI, assessed by calculating the differences in the −2 logarithm likelihood (−2 ln [L]) and area under the curve (AUC), were almost similar.

Relations between dietary sodium and potassium intakes and mortality from cardiovascular disease: the Japan Collaborative Cohort Study for Evaluation of Cancer Risks

BackgroundLimited evidence is available about the relations between sodium and potassium intakes and cardiovascular disease in the general population. ObjectiveThe objective was to investigate relations between sodium and potassium intakes and cardiovascular disease in Asian populations whose mean sodium intake is generally high. DesignBetween 1988 and 1990, a total of 58 730 Japanese subjects (n = 23 119 men and 35 611 women) aged 40–79 y with no history of stroke, coronary heart disease, or cancer completed a lifestyle questionnaire including food intake frequency under the Japan Collaborative Cohort Study for Evaluation of Cancer Risk sponsored by the Ministry of Education, Sports and Science. ResultsAfter 745 161 person-years of follow-up, we documented 986 deaths from stroke (153 subarachnoid hemorrhages, 227 intraparenchymal hemorrhages, and 510 ischemic strokes) and 424 deaths from coronary heart disease. Sodium intake was positively associated with mortality from total stroke, ischemic stroke, and total cardiovascular disease. The multivariable hazard ratio for the highest versus the lowest quintiles of sodium intake after adjustment for age, sex, and cardiovascular disease risk factors was 1.55 (95% CI: 1.21, 2.00; P for trend < 0.001) for total stroke, 2.04 (95% CI: 1.41, 2.94; P for trend < 0.001) for ischemic stroke, and 1.42 (95% CI: 1.20, 1.69; P for trend < 0.001) for total cardiovascular disease. Potassium intake was inversely associated with mortality from coronary heart disease and total cardiovascular disease. The multivariable hazard ratio for the highest versus the lowest quintiles of potassium intake was 0.65 (95% CI: 0.39, 1.06; P for trend = 0.083) for coronary heart disease and 0.73 (95% CI: 0.59, 0.92; P for trend = 0.018) for total cardiovascular disease, and these associations were more evident for women than for men. ConclusionsA high sodium intake and a low potassium intake may increase the risk of mortality from cardiovascular disease.

P.[G576S; E689K]: pathogenic combination or polymorphism in Pompe disease?

We discuss four cases of acid alpha-glucosidase deficiency (EC, 3.2.1.3/20) without evident symptoms of Pompe disease (OMIM No 232300) in individuals of Asian descent. In three cases, the deficiency was associated with homozygosity for the sequence variant c.[1726G>A; 2065G>A] in the acid alpha-glucosidase gene (GAA) translating into p.[G576S; E689K]. One of these cases was a patient with profound muscular atrophy, another had cardio-myopathy and the third had no symptoms. The fourth case, the mother of a child with Pompe disease, was compound heterozygote for the GAA sequence variants c.[1726G>A; 2065G>A]/c.2338G>A (p.W746X) and had no symptoms either. Further investigations revealed that c.[1726A; 2065A] is a common GAA allele in the Japanese and Chinese populations. Our limited study predicts that approximately 4% of individuals in these populations are homozygote c.[1726A; 2065A]. The height of this figure in contrast to the rarity of Pompe disease in Asian populations and the clinical history of the cases described in this paper virtually exclude that homozygosity for c.[1726A; 2065A] causes Pompe disease. As c.[1726A; 2065A] homozygotes have been observed with similarly low acid alpha-glucosidase activity as some patients with Pompe disease, we caution they may present as false positives in newborn screening programs especially in Asian populations.

Association of BACE1 Gene Polymorphism with Alzheimer’s Disease in Asian Populations: Meta-Analysis Including Korean Samples

Background: β-Site amyloid precursor protein cleaving enzyme (BACE) is a candidate risk factor for Alzheimer’s disease (AD) from its key role in β-amyloid generation. Previous genetic association studies of BACE1 gene have yielded conflicting results. This study is an attempt to clarify whether the common SNP in exon 5 of BACE1 (rs638405, Val262) is associated with a risk for late-onset AD. Methods: We genotyped a synonymous C/G polymorphism of BACE1 located in exon 5 and apolipoprotein E (ApoE) in 248 AD patients and 224 healthy persons. A meta-analysis with pooled data from four Chinese studies and our results was performed. Results: The allele and genotype frequencies of BACE1 polymorphism were not significantly different between cases and controls (p > 0.05) in the Korean population. A meta-analysis of previously published Asian populations including Koreans showed evidence of a weak association (p = 0.0555 for genotypes, p = 0.0352 for alleles). However, a significant association between the CC genotype and AD was observed in the ApoE-Ε4-positive groups (p = 0.0044, OR = 1.995; 95% CI = 1.319–3.018). Conclusion: These data suggest that BACE1 polymorphism in exon 5 influences risk for late-onset AD in those carrying the ApoE Ε4 allele.

The PTPN22 promoter polymorphism –1123G&gt;C association cannot be distinguished from the 1858C&gt;T association in a Norwegian rheumatoid arthritis material

The protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene has, during the last 2 years, been recognized as a susceptibility gene for numerous autoimmune diseases, including rheumatoid arthritis (RA) and type 1 diabetes. An association between the exonic 1858C>T single nucleotide polymorphism (SNP) and RA has repeatedly been replicated in several Caucasian populations. The SNP is not associated with autoimmune diseases in Asian populations, as the 1858T allele is almost absent. Recently, a promoter polymorphism -1123G>C was proposed to be associated with acute-onset type 1 diabetes in Japanese and Korean populations. Furthermore, in Caucasian populations, the presence of additional PTPN22 risk variants has been suggested, indicating that the 1858C>T risk variant cannot explain the entire disease association observed in the region. In this study, we wanted to jointly address and integrate these separate findings to further elucidate the association between the PTPN22 gene and RA in a Norwegian material of 861 RA patients and 559 healthy controls. Our results revealed that the strength of the association with the PTPN22 promoter polymorphism, -1123G>C, is analogous to that observed for 1858C>T. As the -1123G>C variant is also polymorphic in Asian populations, our data underpin the need to further explore the association between this variant and autoimmune diseases in different populations.