METHODS: In this study, multi-locus sequence typing (MLST) was performed on clinical B. pseudomallei isolates collected from Kelantan state of Malaysia, patients' clinical data were reviewed and then genotype-risk correlations were investigated.
RESULTS: Genotyping of 83 B. pseudomallei isolates revealed 32 different STs, of which 13(40%) were novel. The frequencies of the STs among the 83 isolates ranged from 1 to 12 observations, and ST54, ST371 and ST289 were predominant. All non-novel STs reported in this study have also been identified in other Asian countries. Based on the MLST data analysis, the phylogenetic tree showed clustering of the STs with each other, as well as with the STs from Southeast Asia and China. No evidence for associations between any of B. pseudomallei STs and clinical melioidosis presentation was detected. In addition, the bacterial genotype clusters in relation with each clinical outcome were statistically insignificant, and no risk estimate was reported. This study has expanded the data for B. pseudomallei on MLST database map and provided insights into the molecular epidemiology of melioidosis in Peninsular Malaysia.
CONCLUSION: This study concurs with previous reports concluding that infecting strain type plays no role in determining disease presentation.
MATERIALS AND METHODS: The EGFR intron 1 polymorphism was analysed in three distinct healthy Asian subjects, namely, Chinese (N = 96), Malays (N = 98) and Indians (N = 100). Comparative genomic hybridisation was performed to investigate for changes in DNA copy number in relation to the polymorphic CA dinucleotide repeats in breast tumor tissues (N = 22).
RESULTS: The frequency of short alleles with 14 and 15 CA repeats were most common in the Asian populations and significantly higher than those reported for Caucasians. The frequency of 20 CA repeats was 5%, almost 13-fold lower than previous reports. EGFR amplifications were detected in 23% and 11% of breast tumor tissues harboring short and long CA repeats, respectively.
CONCLUSION: Our results show that the frequency of alleles encoding for short CA dinucleotide repeats is common in Asian populations. EGFR expression and amplification levels were also higher in Asian breast tumor tissues with short CA dinucleotide repeats. These findings suggest that the EGFR intron 1 polymorphism may influence response to treatment with tyrosine kinase inhibitors in breast cancer patients and further studies are warranted.
METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation.
RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P