Patients Of Different Ethnic Groups Research Articles

Ethnic Differences in the Safety and Efficacy of Tenecteplase Versus Alteplase for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Tenecteplase is a thrombolytic agent with pharmacological advantages over alteplase and has been shown to be noninferior to alteplase for acute ischemic stroke in randomized trials. However, evidence pertaining to the safety and efficacy of tenecteplase in patients from different ethnic groups is lacking. The aim of this systematic review and metaanalysis was to investigate ethnicity-specific differences in the safety and efficacy of tenecteplase versus alteplase in patients with acute ischemic stroke. Following an International Prospective Register of Systematic Reviews (PROSPERO)- registered protocol (CRD42023475038), three authors conducted a systematic review of the PubMed/MEDLINE, Embase, Cochrane Library, and CINAHL databases for articles comparing the use of tenecteplase with any thrombolytic agent in patients with acute ischemic stroke up to November 20, 2023. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two independent authors extracted data onto a standardized data collection sheet. A pairwise meta-analysis was conducted in risk ratios (RR). From 34 studies (59,601 participants), the rate of complete recanalization was significantly higher (P<0.01) in Asian (RR: 1.91, 95% confidence interval [CI]: 1.30 to 2.80) versus Caucasian patients (RR: 0.99, 95% CI: 0.87 to 1.14). However, Asian patients (RR: 1.18, 95% CI: 0.87 to 1.62) had significantly higher (P=0.01) rates of mortality compared with Caucasian patients (RR: 1.10, 95% CI: 1.00 to 1.22). Caucasian patients were also more likely to attain a modified Rankin Scale (mRS) score of 0 to 2 at follow-up (RR: 1.14, 95% CI, 1.10 to 1.19) compared with Asian (RR: 1.00, 95% CI, 0.95 to 1.05) patients. There was no significant difference in the rate of symptomatic intracranial hemorrhage (P=0.20) and any intracranial hemorrhage (P=0.83) between Asian and Caucasian patients. Tenecteplase was associated with significantly higher rates of complete recanalization in Asian patients compared with Caucasian patients. However, tenecteplase was associated with higher rates of mortality and lower rates of mRS 0 to 2 in Asian patients compared with Caucasian patients. It may be beneficial to study the variations in response to tenecteplase among patients of different ethnic groups in large prospective cohort studies.

The Role Of Ethnicity In Heart Failure Outcomes Post Intervention

Significance and Background Heart failure is a continuing epidemic which has become a growing health care burden. Additionally, racial disparities continue to pose a major issue in healthcare with African-Americans being 1.5 times more likely to develop heart failure than their Caucasian counterparts. Aim Considering differences in ethnically-based determinants of health, this study was undertaken to assess outcomes in ethnically different heart failure patients post discharge with respect to hypertension, diabetes, COPD, and renal insufficiency. Methods This is a single center retrospective analyses of data collected from heart failure patients of different ethnic groups in the preceding 24 months. The data collected included survival, left ventricular ejection fraction, BMI, age, gender, renal function, chronic obstructive pulmonary disease (COPD) and diabetes. The outcomes assessed included development of significant comorbidities: hypertension, diabetes, COPD, and renal insufficiency. Results The study population was 46.8% female and 53.2% male, with a mean BMI of 31.1 (obese). Hispanic patients tend to develop diabetes more than their white counterparts post intervention/discharge (p<.001). People of multiple ethnicities were most likely to develop hypertension post discharge (p=.0047). In contrast, non-Hispanic White patients were most likely to have COPD before intervention (p<.001), and to develop COPD after CHF discharge (p<.001). Conclusions The single center patient data presented here reflects racial and ethnic disparities in patients post- CHF intervention, in addition to a dangerously elevated average BMI. Racial and ethnic differences in risk of developing comorbidities post-intervention must be considered in treatment. Identification of such ethnic differences in outcomes despite intervention could possibly pave the way to develop targeted therapies in an era of personalized medicine. Heart failure is a continuing epidemic which has become a growing health care burden. Additionally, racial disparities continue to pose a major issue in healthcare with African-Americans being 1.5 times more likely to develop heart failure than their Caucasian counterparts. Considering differences in ethnically-based determinants of health, this study was undertaken to assess outcomes in ethnically different heart failure patients post discharge with respect to hypertension, diabetes, COPD, and renal insufficiency. This is a single center retrospective analyses of data collected from heart failure patients of different ethnic groups in the preceding 24 months. The data collected included survival, left ventricular ejection fraction, BMI, age, gender, renal function, chronic obstructive pulmonary disease (COPD) and diabetes. The outcomes assessed included development of significant comorbidities: hypertension, diabetes, COPD, and renal insufficiency. The study population was 46.8% female and 53.2% male, with a mean BMI of 31.1 (obese). Hispanic patients tend to develop diabetes more than their white counterparts post intervention/discharge (p<.001). People of multiple ethnicities were most likely to develop hypertension post discharge (p=.0047). In contrast, non-Hispanic White patients were most likely to have COPD before intervention (p<.001), and to develop COPD after CHF discharge (p<.001). The single center patient data presented here reflects racial and ethnic disparities in patients post- CHF intervention, in addition to a dangerously elevated average BMI. Racial and ethnic differences in risk of developing comorbidities post-intervention must be considered in treatment. Identification of such ethnic differences in outcomes despite intervention could possibly pave the way to develop targeted therapies in an era of personalized medicine.

Modern views on the role of X gene of the hepatitis B virus (Hepadnaviridae: Orthohepadnavirus: Hepatitis B virus) in the pathogenesis of the infection it causes

The review presents information on the role of hepatitis B virus (Hepadnaviridae: Orthohepadnavirus: Hepatitis B virus) (HBV) X gene and the protein it encodes (X protein) in the pathogenesis of viral hepatitis B. The evolution of HBV from primordial to the modern version of hepadnaviruses (Hepadnaviridae), is outlined as a process that began about 407 million years ago and continues to the present. The results of scientific works of foreign researchers on the variety of the influence of X protein on the infectious process and its role in the mechanisms of carcinogenesis are summarized. The differences in the effect of the X protein on the course of the disease in patients of different ethnic groups with regard to HBV genotypes are described. The significance of determining the genetic variability of X gene as a fundamental characteristic of the virus that has significance for the assessment of risks of hepatocellular carcinoma (HCC) spread among the population of the Russian Federation is discussed.

Investigation on the etiology of patients undergoing non-traumatic total hip arthroplasty in China.

China has neither a nationwide joint replacement registry similar to Sweden and New Zealand nor a universal healthcare (medical insurance) registry similar to Hong Kong and Singapore to check. The purpose was to initially understand the distribution characteristics of gender, age and etiology of patients undergoing total hip replacement for non-traumatic reasons nationwide. The clinical data of patients who underwent initial artificial total hip replacement due to non-traumatic reasons in joint surgery of 13 large general first-class hospitals at Grade 3 in northern, western, eastern, southern, and southwestern China were collected. After the classification of patients by gender, the etiological characteristics and age distribution of male and female patients were compared, as well as male to female ratio and disease composition ratio of patients of different ages, distribution of causes in different regions, composition ratio, and age distribution characteristics of patients of different ethnic groups. In this study, the data of a total of 7663 patients in joint surgery of 13 general first-class hospitals at Grade 3 from 2015 to 2017 were collected, and 7622 patients were finally included in the study after excluding missing age, gender and some foreign patients. The main causes of diagnosis in male patients were AVN, DDH, and OA, and top 3 causes in female patients were DDH, AVN, and OA. This study initially understand the distribution characteristics of gender, age and etiology of patients undergoing total hip replacement for non-traumatic reasons nationwide, and further guide the clinical diagnosis, early prevention and treatment of the disease and provide data.

Biological profile of medical response in alcoholic patients of different ethnic groups in Siberia

IntroductionThe individual sensitivity of a person to the effects of alcohol is defined as the possibility of adaptive reactions, which are controlled by various factors associated in their manifestation with characteristics in various ethnic populations.ObjectivesTo determine biological profile of medical response in alcoholic patients of different ethnic groups.Methods168 alcoholic men, aged 17 to 62 years were examined. For the therapeutic correction of withdrawal and post-withdrawal symptoms of patients from two different ethnic groups (Tatars and Russians in Siberia), the original anticonvulsant galodif (M-chloro-benzhydrylurea) was used. Pharmacokinetic parameters were calculated a model-independent method of statistical moments: half-life (T1/2,h), total clearance (Clt,ml/min), average time of the residual drug in the body (MRI,h), average elimination time (MET,h), the area under the pharmacokinetic curve (AUC, μg/ml).ResultsGalodif causes a reduction in almost half T1/2, a significant decrease in the average time of the residual drug in the body MRI, and the average elimination time MET. Overall clearance increased. Under the influence of the course with Galodif, antipyrine elimination intensified, which indicates the induction of the cytochrome P-450 system of microsomal liver monooxygenases in Russian alcoholic patients. Galodif causes a reduction of almost five-fold T1/2, a significant decrease MRI and MET. Activation of oxidative metabolism of xenobiotics in Tatar alcoholic patients is more significant.ConclusionsThe increased sensitivity of P-450 cytochrome system to anticonvulsants action with inductive detoxification properties reflects differences in adaptive mechanisms in human from various ethnic groups, what is significant in the therapy.DisclosureNo significant relationships.

Association of Interleukin-10 Gene Polymorphisms with Ulcerative Colitis

This literature review is devoted to the study of the role of polymorphic variants of the anti-inflammatory interleukin-10 gene (Interleukin-10, IL10) in the etiology and pathogenesis of ulcerative colitis in patients of various ethnic groups. Aim . To generalize the results obtained from electronic databases on the study of the characteristics of the course of ulcerative colitis in patients of different ethnic groups, taking into account the carriage of IL10 gene polymorphisms. Materials and methods . Twenty-five studies were selected, including four meta-analyzes devoted to the study of associative relationships of single nucleotide polymorphisms (SNPs) of the IL10 gene isolated from blood samples at positions -592AA/CA, -819CT, -1082АА/GA, and rs3024505 in the development and course of ulcerative colitis. Results. A number of researchers from Europe, Saudi Arabia report an increased incidence of ulcerative colitis among carriers of the IL10-1082AA SNP and a low incidence among carriers of -592AA. Positive associations of IL10-819CT with the prevalence of ulcerative colitis are presented in single reports from Europe, the Middle East and in a number of studies from Asian countries. However, the identified associations, even within the same population, are often contradictory. Perhaps the discrepancies are due to the ethnic heterogeneity of the groups in the considered cohorts, and therefore it is necessary to continue epidemiological studies with a large sample size in specific geographic areas.

Improving Prostate Cancer (PCa) Classification Performance by Using Three-Player Minimax Game to Reduce Data Source Heterogeneity.

PCa is a disease with a wide range of tissue patterns and this adds to its classification difficulty. Moreover, the data source heterogeneity, i.e. inconsistent data collected using different machines, under different conditions, by different operators, from patients of different ethnic groups, etc., further hinders the effectiveness of training a generalized PCa classifier. In this paper, for the first time, a Generative Adversarial Network (GAN)-based three-player minimax game framework is used to tackle data source heterogeneity and to improve PCa classification performance, where a proposed modified U-Net is used as the encoder. Our dataset consists of novel high-frequency ExactVu ultrasound (US) data collected from 693 patients at five data centers. Gleason Scores (GSs) are assigned to the 12 prostatic regions of each patient. Two classification tasks: benign vs. malignant and low- vs. high-grade, are conducted and the classification results of different prostatic regions are compared. For benign vs. malignant classification, the three-player minimax game framework achieves an Area Under the Receiver Operating Characteristic (AUC) of 93.4%, a sensitivity of 95.1% and a specificity of 87.7%, respectively, representing significant improvements of 5.0%, 3.9%, and 6.0% compared to those of using heterogeneous data, which confirms its effectiveness in terms of PCa classification.

Determination the Effects of Hyperthyroidism on Pre-Eclampsia in Women of Balochistan

Thyroid gland is an endocrine gland that reproduces hormones that regulates the body metabolic rate and other body functions. Hyperthyroidism is the dysfunction of thyroid gland which interferes during 2nd and 3rd trimester of pregnancies inducing pre-eclamptic disorder in pregnant women. These disorders may cause deaths as well as morbidity losses in mothers and fetus. These conditions are observed due to imbalance production of T3, T4 and TSH. Hyperthyroidism is highly associated with the onset of pre-eclampsia. Pre-eclampsia is detected by elevated levels of proteinuria as well as systolic and diastolic blood pressures. This study was conceded to discover the influence of hyperthyroidism on pre-eclamptic women of Balochistan. For the purpose, one hundred one (101) pregnant women of 15-50 years of age were selected for this study for comprehensive history, physical and medical examination according to the inclusion and exclusion criteria. Patients of different ethnic groups were examined at Out Patient Department (OPD) in Centre for Nuclear Medicine and Radio therapy (CENAR), Sandeman Provincial Hospital and Bolan Medical Complex hospital (BMC), Quetta. The study focuses on the identification of factors associated with hyperthyroidism and pre-eclampsia and to create awareness regarding this important health issue during pregnancy which may lead to eclamptic seizures during onset of full term labor and are found to be fatal for women and neonate during pregnancy. The current study revealed that out of 101 hyperthyroid patients 61.4% and 20.8% patients belong to Pashtoon and Baloch ethnic groups respectively. It was also found that 44 out of 101 patients lie in age group of 26-35 years. It was observed that highly educated, socioeconomic sound women developed less Pre-eclampsia. Pre-eclampsia was found to be in a significant numbers (33), in hyperthyroid patients, with highest frequency of Pedal edema (36.6%).

Distribution of HLA-B*27 Subtypes in Patients with Ankylosing Spondylitis in Local Population.

To compare the distribution of HLA-B*27 subtypes in healthy controls and in ankylosing spondylitis (AS) patients of different ethnic groups from Pakistan. Descriptive study. Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from April 2016 to October 2017. Forty-nine HLA-B*27 positive, unrelated AS patients and 18 HLA-B*27 positive healthy BMT/renal transplant donors were selected for this study. Typing of the HLA-B27 alleles was performed by the polymerase chain reaction-sequence-specific primer (PCR-SSP). There was a wide number of HLA-B*27 subtypes and an elevated frequency of the B*2707 allele in the AS patients. The allele B*2706 seems to have a protective role in the population studied because it was found only in the healthy controls. HLA-B*27:03 and 07 were found predominant subtypes in Punjabis and Pathans, respectively. There were no significant differences for the distribution of B*27 subtypes between patients and controls (p >0.05).

The association between patient education level and economic status on outcomes following surgical management of (fracture) non-union

BackgroundSocioeconomic disparities are an inherent and currently unavoidable aspect of medicine. Knowledge of these disparities is an essential component towards medical decision making, particularly among an increasingly diverse population. While healthcare disparities have been elucidated in a wide variety of orthopaedic conditions and management options, they have not been established among patients who present for treatment of an ununited fracture. The purpose of this study is to answer the following questions: 1) Following surgical management of (fracture) non-unions, are there differences in outcomes between differing ethnic groups? 2) Following surgical management of (fracture) non-unions, are there differences in outcomes between patients with differing education levels? 3) Following surgical management of (fracture) non-unions, are there differences in outcome between patients with differing incomes? MethodsBetween September 2004 and December 2017, operatively treated patients who presented with a long bone fracture non-union were prospectively followed. These patients presented with a variety of fracture non-unions that underwent surgical intervention. Sociodemographic factors were recorded at presentation. Long-term outcomes were evaluated using the Short Musculoskeletal Function Assessment (SMFA), pain scores, post-operative complications and physical exam at latest follow up. The SMFA is a 46-item questionnaire, assessing patient functional and emotional response to musculoskeletal ailments. ResultsThree-hundred-twenty-nine patients met inclusion criteria. Patients with a lower education had worse long-term functional outcomes (P < 0.001) and increased pain scores (P = 0.002) at latest follow-up. Patients who made less than $50,000 annually had worse long-term functional outcomes (P = 0.002) and reported higher pain scores (P = 0.003) following surgical management of (fracture) non-unions. Multiple linear regression demonstrated education level to be an independent predictor of long-term functional outcomes following surgical management of (fracture) non-unions (B= -0.154, 95% Confidence Interval [CI]=-10.96 to -1.26, P = 0.014). No differences existed in outcomes or pain scores between those of different ethnic groups. No differences existed regarding post-operative complications and time to union between patients of different ethnic groups, educational levels and income status. ConclusionPatients with lower education levels and individuals who make less than $50,000 annually have worse functional outcomes following surgical management of (fracture) non-unions. Orthopaedic trauma surgeons should therefore be aware of these disparities, and consider early interventions aimed at optimizing patient recovery in these subsets.

ОСОБЕННОСТИ ПОЛИМОРФИЗМА ГЕНОВ ИЛ-6 (IL-6-174G/C; IL-6-572G/C) У ПАЦИЕНТОВ РАЗЛИЧНЫХ ЭТНИЧЕСКИХ ГРУПП С ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА (ОБЗОР ЛИТЕРАТУРЫ)

Цель исследования. Представить читателю подробный обзор особенностей полиморфизма генов ИЛ-6 у пациентов различных этнических групп с ишемической болезнью сердца (ИБС), а также исследовать влияние разных генотипов однонуклеотидных полиморфизмов интерлейкина ИЛ-6 на циркуляционные уровни воспалительных и противовоспалительных цитокинов у пациентов с различными частотами аллелей с ИБС.Материал и методы исследования. Авторами был проведён поиск литературы об особенностях полиморфизма генов ИЛ-6 у пациентов различных этнических групп с ИБС, с использованием соответствующих ключевых слов, в поисковых системах PubMed и Google Scholar, по базам данных Scopus, Web of Science, MedLine, The Cochrane Library, EMBASE, Global Health, CyberLeninka, РИНЦ и другим.Результаты. Потенциальная связь между полиморфизмами генов ИЛ-6 и ИБС широко исследованы на сегодняшний день, однако результаты исследований остаются непоследовательными и несколько противоречивыми. Наиболее сильная взаимосвязь установлена по генотипам IL-6-174G/C; IL-6-572G/C для различных этнических групп, что и обуславливает интерес изучения в этом направлении в эпоху индивидуализации медицины.Область применения результатов. Организация здравоохранения, кардиология, внутренние болезни, патологическая физиология.

The study of the intranasal parameters in the patients of different ethnic groups deduced from the results of computed tomography

The study of the intranasal parameters in the patients of different ethnic groups deduced from the results of computed tomography

Expression analysis of E-cad and vascular endothelial growth factor in triple-negative breast cancer patients of different ethnic groups in western China

The aim of this article is to investigate the expression of E-cadherin (E-cad) and vascular endothelial growth factor (VEGF) in triple-negative breast cancer (TNBC) of Han and Uygur women patients in western China, and their relationship with clinical features of TNBC.Totally, 172 cases of Han TNBC patients and 79 cases of Uighur TNBC patients were enrolled. The expressions of E-cad and VEGF were detected with immunohistochemistry. The correlation of E-cad and VEGF expression with lymph node metastasis, TNM stage, and histological grade were analyzed. The 5-year disease-free survival rate of the 2 groups was also evaluated.There was no significant difference in the 5-year disease-free survival rate (P > .05) and the expression of E-cad between the 2 groups. The positive rate of VEGF in Han was significantly lower than that in Uygur (P < .05). The expression of E-cad was negatively correlated with lymph node metastasis, TNM stage, and histological grade (−1≤r < 1, P < .05). However, the expression of VEGF was positively correlated with lymph node metastasis and TNM staging (0 < r < 1, P < 0.05), but not with histological grading.The expression of E-cad and VEGF and their relationship with clinical features of TNBC suggest that Uygur TNBC patients might have different prognostic factors as compared with Han patients.

Ethnic differences in clinical outcome of patients presenting to the emergency department with chest pain.

Ethnicity, although known to influence cardiovascular outcome in assorted clinical settings, has not been investigated previously as a risk factor in patients presenting to the emergency department with suspected acute myocardial infarction. In this multi-ethnic cohort study conducted in Singapore and The Netherlands, 2784 patients presenting to the emergency department with chest pain were enrolled (788 Caucasians, 1281 Chinese, 404 Indians and 311 Malays) and were followed up for 1 year. Although Caucasian patients on average were older and had incurred more cardiovascular adverse events, the Asian ethnic groups carried a greater burden of cardiovascular risk factors. Caucasian and Malay patients were most frequently diagnosed with acute myocardial infarction (Caucasians 11.2%, Chinese and Indians 6.4%, Malays 10.6%, P<0.001), also after correction for baseline differences. Chinese and Indian patients, however, more often had unstable angina. Asian patients had strikingly more extensive coronary artery disease than Caucasian patients (triple-vessel disease: Caucasians 6.5%, Chinese 22.8%, Indians 32.4%, Malays 32.8%, P<0.001) and Chinese patients with myocardial infarction more frequently underwent coronary revascularisation compared with Caucasian patients (Caucasians 41.4%, Chinese 67.5%, Indians 62.5%, Malay 46.7%, P=0.005). Ethnicity was not an independent predictor of major adverse cardiovascular events during 1-year follow-up in all chest pain patients. The prevalence of myocardial infarction and unstable angina, revascularisation rate and extent of coronary artery disease differ significantly among chest pain patients of different ethnic groups. These findings have important clinical implications and support consideration of ethnicity in risk stratification and determination of the patient management strategy in patients with symptoms suggestive of myocardial infarction.

Genomic epidemiology of prostate cancer, family history approach, and the adoption of socio-ecological model to increase screening among American adult males

This project compared the deadly impact of prostate cancer in African-Americans and Caucasians and identified the gene-chromosomes which serve as precursors for this type of cancer. Innovative genomic techniques for screening and detecting prostate cancer were discussed. A comprehensive family history approach for screening at risk family members was illustrated. The succinct rationales for the socio-ecological model were presented and the relevance for screening using this model was critically analysed. To ensure that patients receive the precise chemotherapy, the concept of pharmacogenomics was presented as mechanism to ensure that the correct drug is administered in the right dose, at the right time to patients of different ethnic groups, based on their specific DNA sequence in order to avoid the onset of imperfect specificity and iatrogenic diseases. A comprehensive analysis of precision medicine which consists of predictive, preventive, personalised, and participatory innovative approach in genomic medicine was presented. Molecular science was predicted to enable oncologists to maximise treatment effectiveness while avoiding potentially life-threatening side-effects.

Association of Asian ethnicity with disease activity in SLE: an observational study from the Monash Lupus Clinic

Systemic lupus erythematosus (SLE), an autoimmune condition with diverse clinical manifestations, is reported to have different expression in populations of different ancestry. Most previous studies compared patients of different ethnic groups from geographically distinct cohorts. In our study, we aimed to characterize disease manifestations in patients of different ethnic groups from a single centre, and studied patterns of disease activity over time. Demographics, baseline disease characteristics and autoantibody profiles, and disease activity (SLEDAI) measured at each visit, were captured from all consenting patients prospectively followed between 2007 and 2011 in an urban teaching hospital lupus clinic. Ethnicity was self-reported. Asian ethnicity was significantly associated with more clinically severe SLE. Time-adjusted mean SLEDAI (p = 0.01) and maximum SLEDAI (p = 0.0018) were significantly higher in Asian patients. Asians were more likely to have renal disease (OR 2.9, 95% CI 1.4-5.98; p = 0.004) and persistently active disease (PAD) (OR 2.14, 95% CI 1.05-4.38, p = 0.04). Asian lupus patients also had a significantly higher proportion of autoantibody positivity to anti-dsDNA, anti-RNP, anti-Sm, anti-Ro and anti-La, as well as increased likelihood of hypocomplementaemia and immunosuppressant use. In this single-cohort study, Asian ethnicity was found to be associated with increased SLE disease activity. This suggests significant inter-ethnic genetic contributions to the regulation of autoimmune responses and disease severity in SLE.

Meta-Analysis of Cytochrome P450 2C19 Polymorphism and Risk of Adverse Clinical Outcomes Among Coronary Artery Disease Patients of Different Ethnic Groups Treated With Clopidogrel

Loss-of-function (LOF) variants of cytochrome P450 2C19 (CYP2C19) have been hypothesized to be associated with lesser degrees of platelet inhibition and increased risk for recurrent ischemic events in patients with coronary artery disease on clopidogrel therapy; however, studies from Western countries have yielded mixed results. We aimed to assess the impact of CYP2C19 LOF variants on clinical outcomes from different ethnic groups. Sixteen prospective cohort studies including 7,035 patients carrying ≥ 1 CYP2C19 LOF allele and 13,750 patients with the wild-type genotype were included in this meta-analysis. Carriers of ≥ 1 CYP2C19 LOF allele were at significantly higher risk for adverse clinical events compared to noncarriers during clopidogrel therapy (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.13 to 1.78). The summary OR showed a significant association between CYP2C19 LOF variants and an increased risk of cardiac death (OR 2.18, 95% CI 1.37 to 3.47), myocardial infarction (OR 1.42, 95% CI 1.12 to 1.81), and stent thrombosis (OR 2.41, 95% CI 1.76 to 3.30). Stratified analysis by ethnicity of study population suggested higher odds of adverse clinical events in the Asian population with LOF variants of CYP2C19 (OR 1.89, 95% CI 1.32 to 2.72) compared to Western populations (OR 1.28, 95% CI 1.00 to 1.64). In conclusion, carrier status for LOF CYP2C19 is associated with an increased risk of adverse clinical events in patients with coronary artery disease on clopidogrel therapy despite differences in clinical significance according to ethnicity.

HMLH1 promoter methylation and JC virus T antigen presence in the tumor tissue of colorectal cancer Israeli patients of different ethnic groups

Hypermethylation of tumor suppressor genes' promoter and JC virus infection may be etiologic factors in the development of colorectal cancer (CRC). To look at both JC virus T antigen and hMLH1 promoter methylation in CRC tissue in Israeli ethnic groups with different incidence of CRC. Twenty-four consecutive patients with sporadic CRC were included in the study. Genomic DNA was isolated from paraffin-embedded microdomains removed from five slides of 7 mum by deparaffinizing in multiple xylene washes. Isolated DNA was used as a template for PCR to amplify DNA sequences coding the amino terminus of JC virus T antigen. Methylation-specific PCR was performed on bisulfite-modified DNA templates from CRC tissue materials to study methylation status of hMLH1 promoter, using two sets of primers specific for amplification of methylated and unmethylated alleles. hMLH1 promoter methylation was observed in five patients (20.8%) who were also positive for JC virus T antigen, with even distribution among the ethnic groups. JC virus T antigen DNA was found in cancer tissues of 20 of the 24 patients; 50, 90.9, and 100% of Asia-Africa-born Jews, Europe-America-born Jews, and Israeli Arabs, respectively (P = 0.036 between the first group to the other). Evidence for higher JC virus infection was shown among Europe-America-born Jews and Israeli Arabs. hMLH1 promoter methylation was evenly distributed between different ethnic groups in Israel.

Genetic risk factors for rheumatoid arthritis differ in caucasian and Korean populations

Recent studies have identified a number of novel rheumatoid arthritis (RA) susceptibility loci in Caucasian populations. The aim of this study was to determine whether the genetic variants at 4q27, 6q23, CCL21, TRAF1/C5, and CD40 identified in Caucasians are also associated with RA in a Korean case-control collection. We also comprehensively evaluated the genetic variation within PTPN22, a well-established autoimmune disease-associated gene. We designed an experiment to thoroughly evaluate the PTPN22 linkage disequilibrium region, using tag single-nucleotide polymorphisms (SNPs) and disease-associated SNPs at 5 RA-associated loci recently identified in Caucasians, in 1,128 Korean patients with RA and 1,022 ethnically matched control subjects. We also resequenced the PTPN22 gene to seek novel coding variants that might be contributing to disease in this population. None of the susceptibility loci identified in Caucasian patients with RA contributed significantly to disease in Koreans. Although tag SNPs covering the PTPN22 linkage disequilibrium block were polymorphic, they did not reveal any disease association, and resequencing did not identify any new common coding region variants in this population. The 6q23 and 4q27 SNPs assayed were nonpolymorphic in this population, and the TRAF1/C5, CD40, and CCL21 SNPs did not show any evidence for association with RA in this population of Korean patients. The genetic risk factors for RA are different in Caucasian and Korean patients. Although patients of different ethnic groups share the HLA region as a major genetic risk locus, most other genes shown to be significantly associated with disease in Caucasians appear not to play a role in Korean patients with RA.

WGA Allows the Molecular Characterization of a Novel Large CFTR Rearrangement in a Black South African Cystic Fibrosis Patient

By performing extensive scanning of whole coding and flanking sequences of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene, we had previously identified the CF-causing mutations in black South African patients of different ethnic groups suspected with the disease. Of ten samples analyzed, there were six remaining that had either one (n = 2) or two (n = 4) unidentified CFTR alleles that have now been tested for large rearrangements using a semiquantitative fluorescent PCR assay. A novel deletion encompassing CFTR exon 2 was detected in one patient who was heterozygous for the mutation 3120+1G>A. The Caucasian deletion involving the same exon [c.54-5811_c.164+2186del8108ins182] was ruled out. The DNA had been stored for more than 12 years and only minute quantities remained. We thus used a whole-genome amplification method based on multiple displacement amplification to generate sufficient amounts of DNA to characterize the intronic breakpoints and identify the deletion at the genomic level. Mapping and sequencing the breakpoint junctions revealed a novel large deletion [c.54-1161_c.164+1603del2875]. We have designed a simple test to specifically detect the presence or absence of this large rearrangement. This study reports the first large CFTR rearrangement in a black South African CF patient, further defining the molecular spectrum of CF that will be useful for improving genetic testing and counseling in this region.