Introduction: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer. Methods: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade. Results: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01). Conclusion: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity.
ethnic variation

OBJECTIVETo explore the relationship between the polymorphisms of microRNA genes and the risk of breast cancer, and to analyze molecular markers which can be used in screening of susceptible population.

METHODSAll the individuals included in this case-control study were genetically independent ethnic Han Chinese. The breast cancer patient group consisted of 384 women confirmed by histopathology, and the control group consisted of 192 healthy female individuals. We screened genetic variants in all miRNA genes according to the public database miRBase and NCBI database. A total of twenty-three common single nucleotide polymorphisms in twenty-two miRNAs, which tagged the known common variants with minor allele frequency greater than 0.05 were genotyped. A MassARRAY ® MALDI-TOF system was used for genotyping the candidate SNPs by the method described in the Sequenom Genotyping Protocol. The frequencies of SNPs were compared between cancer cases and controls to identify the SNPs associated with breast cancer susceptibility. Logistic regression analysis was applied to analyze the differences in genotype or allele frequencies of individual SNPs in cancer cases and controls, and to evaluate the correlation between candidate loci and breast cancer risk.

RESULTSThe median age of the total group including 384 breast cancer patients and 192 control subjects was 48 years (range, 21-81 years). There were no significant differences in age distribution (P = 0.695) and smoking status (P = 0.193) between the case group and the control group. However, the number of patients with a family history of breast cancer or ovarian cancer in the case group was significantly higher than that in the control group (9.1% vs.1.6%, P < 0.001). The number of the patients with menarche age below 14 years in the case group was significantly higher than that in the control group (53.1% vs.37.5%, P < 0.001). The number of premenopausal patients in the case group was significantly higher than that in the control group (61.2% vs. 50.0%, P = 0.007). There was no significant association between breast cancer risk and the single nucleotide polymorphisms in miRNA genes (P > 0.05).

CONCLUSIONSThe genetic polymorphism of miRNA is not obviously associated with breast cancer risk among Chinese women.

Adult ; Aged ; Aged, 80 and over ; Alleles ; Asian Continental Ancestry Group ; Breast Neoplasms ; genetics ; Case-Control Studies ; China ; Ethnic Groups ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genetic Variation ; Genotype ; Humans ; Menarche ; MicroRNAs ; Middle Aged ; Ovarian Neoplasms ; genetics ; Polymorphism, Single Nucleotide ; Regression Analysis ; Risk

Asian populations contain a variety of ethnic groups that have ethnically specific genetic differences. Ethnic variants may be highly relevant in disease and human differentiation studies. Here, we identified ethnically specific variants and then investigated their distribution across Asian ethnic groups. We obtained 58,960 Pan-Asian single nucleotide polymorphisms of 1,953 individuals from 72 ethnic groups of 11 Asian countries. We selected 9,306 ethnic variant single nucleotide polymorphisms (ESNPs) and 5,167 ethnic variant copy number polymorphisms (ECNPs) using the nearest shrunken centroid method. We analyzed ESNPs and ECNPs in 3 hierarchical levels: superpopulation, subpopulation, and ethnic population. We also identified ESNP- and ECNP-related genes and their features. This study represents the first attempt to identify Asian ESNP and ECNP markers, which can be used to identify genetic differences and predict disease susceptibility and drug effectiveness in Asian ethnic populations.
Asian Continental Ancestry Group ; Classification ; Disease Susceptibility ; DNA Copy Number Variations ; Ethnic Groups ; Genetic Variation* ; Genotype ; Humans ; Polymorphism, Single Nucleotide

Human carboxylesterase 1 (CES1) is a serine esterase that hydrolyzes various exogenous compounds. Single nucleotide polymorphisms (SNPs) of CES1 may lead to inter-individual metabolic variability of its substrates. The allele and haplotype frequencies of known SNPs have been demonstrated to vary among ethnic groups. We analyzed genetic variations of CES1 in a Korean population. Direct sequencing of all exons and flanking regions of the CES1 gene was performed on samples obtained from 200 Koreans. We identified 41 SNPs. The most frequent SNPs was -914G>C (frequency: 99.5%), followed by 4256G>A (frequency: 65.8%), -75T>G (frequency: 59.3%). Haplotype analysis using the identified SNPs revealed fifteen haplotypes (> or =1% haplotype frequency) in our samples. The most frequent haplotype was Hap1 (frequency: 15.4%). Among the identified 41 SNPs, nine of which are novel variants and 14 SNPs were nonsynonymous variants. Using the functional predictive software PolyPhen-2, the G19V, E221G, and A270S variants were predicted to be most likely damaging to the function and structure of CES1. In-vitro analyses for two of these variants have been previously performed; however, functional evaluation of E221G (11657A>G, rs200707504) still needs to be conducted. Therefore, further studies are warranted to characterize the functional impact of E221G on CES1 activity.
Alleles ; Asian Continental Ancestry Group ; Carboxylesterase* ; Ethnic Groups ; Exons ; Genetic Variation ; Haplotypes ; Humans ; Polymorphism, Genetic* ; Polymorphism, Single Nucleotide ; Serine

OBJECTIVETo study the baseline distribution of polymorphisms in the promoter of peroxisome proliferators activated receptor co-activator 1 (PPARGC1A) gene in ethnic Hans from Beijing, and to assess their association with type 2 diabetes (T2DM).

METHODSA 2-stage study was designed. Firstly, the promoter region of PPAGC1A gene was screened with PCRRFLP in a small population (n=216, T2DM/control: 104/112), which was followed by a replication study of a larger group (n=1546, T2DM/control: 732/814). Fasting plasma glucose, insulin, blood lipid, height, weight, waist circumference, and blood pressure were measured in all subjects. Potential association was assessed by logistic regression. Linkage disequilibrium and haplotype analysis were conducted with Haploview software.

RESULTSFive polymorphisms were identified with Sanger sequencing, among which T-2120C (rs3755857), -1999C/G (rs2946386) and -1437T/C (rs2970870) were included for genotypic analysis based on their moderate levels of heterozygosity. No significant difference was found between the two groups. When adjusted for age and gender confounding, we have combined the OR values from population 1 and population 2 based on Mantel-Haenszel fixed model, and recognized a mild contribution of C allele of -1999C/G (rs2946386) to the 1.18-fold risk of T2DM (P=0.03, OR=118). No haplotype was associated with T2DM after permutation correction.

CONCLUSIONThe C allele of -1999C/G ( rs2946386) in the promoter region of the PPARGC1A gene is mildly associated with T2DM. Variations in the promoter region of the PPARGC1A gene seem not to confer the risk of T2DM in our population.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Blood Glucose ; metabolism ; Case-Control Studies ; China ; ethnology ; Diabetes Mellitus, Type 2 ; blood ; ethnology ; genetics ; Ethnic Groups ; genetics ; Female ; Genetic Variation ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Transcription Factors ; genetics

PURPOSE: The aim of this study is to further understand the status of BRCA1 and BRCA2 mutation among Chinese high-risk breast cancer patients in multiple-ethnic regions of China. METHODS: A total of 79 blood samples of high-risk breast cancer patients from Xinjiang Uyghur autonomous region were analyzed by PCR-DHPLC sequencing analysis. RESULTS: Analysis with full length of the two genes identified a total of 6 deleterious mutations (2073delA, 2394C-T [Q759X] and IVS16+1G>A in BRCA1; 1627A-T [K467X], 6873delCTCC and 9481delA in BRCA2) in this cohort. The prevalence of BRCA1/2 germline mutation was about 7.6% (6/79) in the Xinjiang multiple ethnic region of China. Among them, 3 novel deleterious mutations, 2073delA in BRCA1 (Han ethnic Chinese) and BRCA2 variants 6873delCTCC and 9481delA (both are Kazakh ethnic Chinese), were identified and they had never been reported in breast cancer information core (BIC) database before. 2394C-T (Q759X) and IVS16+1G>A, in BRCA1 and BRCA2 variants 1627A-T were previously reported in other populations but not Chinese. Among 6 of the BRCA-related tumors, three BRCA1- and one BRCA2-associated tumors were in triple negative (estrogen receptor, progesterone receptor, and HER2 negative expressed) status and exhibited a high tumor grade. So far none of these 6 deleterious mutations were reported in ethnic Han Chinese. CONCLUSION: BRCA germline mutation in Chinese multiple ethnicity region may exhibit different genotypes compared to ethnic Han Chinese in other regions. These differences may arise from interaction of genetic background and environmental factors.
Asian Continental Ancestry Group ; Breast ; Breast Neoplasms ; China ; Cohort Studies ; Ethnic Groups ; Female ; Genetic Variation ; Genotype ; Germ-Line Mutation ; Humans ; Prevalence ; Receptors, Progesterone

INTRODUCTIONRecently, there has been increasing evidence that genetic variation in the angiotensin-converting enzyme (ACE) plays an important role in myocardial infarction. Therefore, the present study was carried out with the aim of investigating the association of the ACE gene insertion/deletion (I /D) polymorphism and its levels in myocardial infarction patients and their first-degree relatives (FDRs).

METHODS206 patients with myocardial infarction, 168 FDRs and 210 control subjects were enrolled in the study. ACE I /D polymorphism was determined using the polymerase chain reaction method. Serum ACE levels were measured using the photometric method.

RESULTSThe DD genotype and ACE activity were significantly higher in patients (p-value is 0.00006 and 0.0001, respectively) and FDRs (p-value is 0.003 and 0.04, respectively) compared with the controls.

CONCLUSIONACE DD genotype and ACE levels are important risk factors for myocardial infarction. This study indicates that the higher frequency of the DD genotype and ACE levels observed in FDRs may increase susceptibility to developing myocardial infarction.

Alleles ; Case-Control Studies ; Chi-Square Distribution ; Confidence Intervals ; Ethnic Groups ; genetics ; Female ; Genetic Predisposition to Disease ; epidemiology ; Genetic Variation ; Genotype ; Humans ; Incidence ; India ; epidemiology ; Male ; Myocardial Infarction ; epidemiology ; genetics ; physiopathology ; Odds Ratio ; Peptidyl-Dipeptidase A ; analysis ; genetics ; Polymorphism, Genetic ; Reference Values

OBJECTIVETo investigate the sequence polymorphism of mtDNA coding region encompassing nt3954-4506 in the Korean Chinese population of Yanbian area.

METHODSPolymerase chain reaction (PCR) and direct sequencing method were used to detect the haplotype distribution of mtDNA coding region in 198 Korean Chinese individuals.

RESULTSTwenty-one haplotypes were observed in the 198 unrelated individuals. The genetic diversity was 0.5906 and the random match probability was 0.4124. Compared with the Andersonos sequence, 19 nucleotide variants were found, of which 14 were previously registered in MITOMAP, and 5 were novel.

CONCLUSIONThe obtained data suggest that these sequence polymorphisms are valuable genetic markers for personal identification when combined with mtDAN control region investigation, thus could be used as basic data for the forensic application in Korean Chinese population.

Asian Continental Ancestry Group ; genetics ; China ; DNA, Mitochondrial ; genetics ; Ethnic Groups ; genetics ; Genetic Variation ; Haplotypes ; Humans ; Korea ; ethnology ; Open Reading Frames ; genetics ; Polymorphism, Genetic ; Sequence Analysis, DNA

OBJECTIVETo analyze the sequence polymorphisms of mitochondrial DNA HVR I and HVR II in Tibetan population in Changdu area of Tibet.

METHODSmtDNAs obtained from 97 unrelated individuals were amplified and directly sequenced.

RESULTSOne hundred and eleven variable sites were identified, including nucleotide transitions, transversions, insertions and deletions. In HVR I region (nt16024-nt16365), sixty-eight polymorphic sites and 92 haplotypes were observed, and the genetic diversity was 0.9985. In HVR II region (nt73-nt340), forty-three polymorphic sites and 91 haplotypes were detected, and the genetic diversity was 0.9882. The random match probability of HVR I and HVR II regions were 0.0120 and 0.0118, respectively. When the sequence analysis of HVR I and HVR II regions were combined, ninety-seven different haplotypes were found. The combined match probability of two unrelated persons having the same sequence was 0.0103.

CONCLUSIONThere are some unique polymorphic loci in the Changdu Tibetan population. The results suggest that there are significant difference in the genetic structure in the mitochondrial DNA D-loop region between Changdu Tibetans and other Asian populations and Caucasians. Sequence polymorphism in mitochondrial DNA HVR I and HVR II can be used as a genetic marker for forensic individual identification and genetic analysis.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; DNA, Mitochondrial ; genetics ; Ethnic Groups ; genetics ; Female ; Genetic Variation ; Genomics ; Haplotypes ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Polymorphism, Genetic ; Sequence Analysis, DNA ; Tibet

OBJECTIVETo investigate the genetic polymorphisms of 11 Y-chromosomal short tandem repeats (STR) loci in Chongqing Tujia population, and to evaluate their forensic application values and genetic relationships with the other 16 populations of China.

METHODSEleven Y-STR loci in 215 unrelated Tujia individuals from Chongqing were amplified with PowerPlex Y System, and the PCR products were analyzed by 310 Genetic Analyzer. Cluster analysis and phylogenic trees were applied to show the genetic distance among the populations.

RESULTSA total of 195 haplotypes were identified and the overall haplotypes diversity for the 11 Y-STR loci was 0.9942. The gene diversity values (GD) for each locus ranged from 0.3757 (DYS391) to 0.9170 (DYS385a/b). Comparing with other 16 populations, the genetic distance between Tujia and Tibetan was the nearest (0.02467), that between the Tujia and Korean ethnic groups was the farthest (0.25350).

CONCLUSIONThe genetic distribution of the 11 Y-STR loci in Chongqing Tujia population showed favorable polymorphisms. They are suitable for forensic identification and paternity testing in the local area. The study of genetic diversity among different populations is useful in understanding their origins, migrations and their relationships.

China ; ethnology ; Chromosomes, Human, Y ; Ethnic Groups ; ethnology ; genetics ; Genetic Variation ; Humans ; Male ; Microsatellite Repeats ; genetics ; Polymorphism, Genetic ; Population Groups ; genetics