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Differences in allele frequencies of autosomal dominant hypercholesterolemia SNPs in the Malaysian population

Alex L, Chahil JK, Lye SH, Bagali P, Ler LW

J Hum Genet, 2012 Jun;57(6):358-62.
PMID: 22534770 DOI: 10.1038/jhg.2012.34

Hypercholesterolemia is caused by different interactions of lifestyle and genetic determinants. At the genetic level, it can be attributed to the interactions of multiple polymorphisms, or as in the example of familial hypercholesterolemia (FH), it can be the result of a single mutation. A large number of genetic markers, mostly single nucleotide polymorphisms (SNP) or mutations in three genes, implicated in autosomal dominant hypercholesterolemia (ADH), viz APOB (apolipoprotein B), LDLR (low density lipoprotein receptor) and PCSK9 (proprotein convertase subtilisin/kexin type-9), have been identified and characterized. However, such studies have been insufficiently undertaken specifically in Malaysia and Southeast Asia in general. The main objective of this study was to identify ADH variants, specifically ADH-causing mutations and hypercholesterolemia-associated polymorphisms in multiethnic Malaysian population. We aimed to evaluate published SNPs in ADH causing genes, in this population and to report any unusual trends. We examined a large number of selected SNPs from previous studies of APOB, LDLR, PCSK9 and other genes, in clinically diagnosed ADH patients (n=141) and healthy control subjects (n=111). Selection of SNPs was initiated by searching within genes reported to be associated with ADH from known databases. The important finding was 137 mono-allelic markers (44.1%) and 173 polymorphic markers (55.8%) in both subject groups. By comparing to publicly available data, out of the 137 mono-allelic markers, 23 markers showed significant differences in allele frequency among Malaysians, European Whites, Han Chinese, Yoruba and Gujarati Indians. Our data can serve as reference for others in related fields of study during the planning of their experiments.
Fulltext Evaluation of quality of DNA extracted from buccal swabs for microarray based genotyping

Livy A, Lye S, Jagdish CK, Hanis N, Sharmila V, Ler LW, et al.

Indian J Clin Biochem, 2012 Jan;27(1):28-33.
PMID: 23277709 DOI: 10.1007/s12291-011-0154-y

Buccal cell usage has been shown by many to be a cost effective and safe method to isolate DNA for various biological experiments especially large epidemiological studies (Garcia-Closas et al. Cancer Epidemiol Biomarkers Prev 10:687-696, 2001). Non-invasive DNA collection methods are preferred over phlebotomy in order to increase study participation and compliance in research centers and for sick patients in hospital settings. There have been conflicting reports about the methodology and results obtained from using buccal DNA. It is not very clear if phlebotomy can be confidently replaced by buccal cell DNA. It is often left for the user to take an intelligent decision. To address this issue, we compared the performance of buccal and blood DNA from same subjects in a genotyping experiment and this paper reports the results. Cotton swab derived buccal cells were scraped from the inner side of cheeks from 16 subjects, and blood was also drawn from the same 16 subjects participating in a genotypic association study of a lipid disease. The DNA quality was assessed by resolving on agarose gels, checking purity (A260/A280) and finally by microarray hybridization. This study showed that DNA degradation affects the total yield and performance of the buccal DNA when compared to the blood DNA in microarray based genotyping. Genotyping results can be seriously compromised if care is not taken to check the quality and yields of such specimens.
Application of streptavidin mass spectrometric immunoassay tips for immunoaffinity based antibody phage display panning

Chin CF, Ler LW, Choong YS, Ong EB, Ismail A, Tye GJ, et al.

J Microbiol Methods, 2016 Jan;120:6-14.
PMID: 26581498 DOI: 10.1016/j.mimet.2015.11.007

Antibody phage display panning involves the enrichment of antibodies against specific targets by affinity. In recent years, several new methods for panning have been introduced to accommodate the growing application of antibody phage display. The present work is concerned with the application of streptavidin mass spectrometry immunoassay (MSIA™) Disposable Automation Research Tips (D.A.R.T's®) for antibody phage display. The system was initially designed to isolate antigens by affinity selection for mass spectrometry analysis. The streptavidin MSIA™ D.A.R.T's® system allows for easy attachment of biotinylated target antigens on the solid surface for presentation to the phage library. As proof-of-concept, a domain antibody library was passed through the tips attached with the Hemolysin E antigen. After binding and washing, the bound phages were eluted via standard acid dissociation and the phages were rescued for subsequent panning rounds. Polyclonal enrichment was observed for three rounds of panning with five monoclonal domain antibodies identified. The proposed method allows for a convenient, rapid and semi-automated alternative to conventional antibody panning strategies.
Association of genetic and non-genetic risk factors with the development of prostate cancer in Malaysian men

Munretnam K, Alex L, Ramzi NH, Chahil JK, Kavitha IS, Hashim NA, et al.

Mol Biol Rep, 2014;41(4):2501-8.
PMID: 24443231 DOI: 10.1007/s11033-014-3107-8

There is growing global interest to stratify men into different levels of risk to developing prostate cancer, thus it is important to identify common genetic variants that confer the risk. Although many studies have identified more than a dozen common genetic variants which are highly associated with prostate cancer, none have been done in Malaysian population. To determine the association of such variants in Malaysian men with prostate cancer, we evaluated a panel of 768 SNPs found previously associated with various cancers which also included the prostate specific SNPs in a population based case control study (51 case subjects with prostate cancer and 51 control subjects) in Malaysian men of Malay, Chinese and Indian ethnicity. We identified 21 SNPs significantly associated with prostate cancer. Among these, 12 SNPs were strongly associated with increased risk of prostate cancer while remaining nine SNPs were associated with reduced risk. However, data analysis based on ethnic stratification led to only five SNPs in Malays and 3 SNPs in Chinese which remained significant. This could be due to small sample size in each ethnic group. Significant non-genetic risk factors were also identified for their association with prostate cancer. Our study is the first to investigate the involvement of multiple variants towards susceptibility for PC in Malaysian men using genotyping approach. Identified SNPs and non-genetic risk factors have a significant association with prostate cancer.
Identification of genetic and non-genetic risk factors for nasopharyngeal carcinoma in a Southeast Asian population

Nor Hashim NA, Ramzi NH, Velapasamy S, Alex L, Chahil JK, Lye SH, et al.

Asian Pac J Cancer Prev, 2012;13(12):6005-10.
PMID: 23464394

BACKGROUND: Nasopharyngeal carcinoma (NPC) is endemic in Southern Chinese and Southeast Asian populations. Geographical and ethnic clustering of the cancer is due to genetic, environmental, and lifestyle risk factors. This case-control study aimed to identify or confirm both genetic and non-genetic risk factors for NPC in one of the endemic countries, Malaysia.
MATERIALS AND METHOD: A panel of 768 single-nucleotide polymorphisms (SNPs) previously associated with various cancers and known non-genetic risk factors for NPC were selected and analyzed for their associations with NPC in a case-control study.
RESULTS: Statistical analysis identified 40 SNPs associated with NPC risk in our population, including 5 documented previously by genome-wide association studies (GWAS) and other case-control studies; the associations of the remaining 35 SNPs with NPC were novel. In addition, consistent with previous studies, exposure to occupational hazards, overconsumption of salt-cured foods, red meat, as well as low intake of fruits and vegetables were also associated with NPC risk.
CONCLUSIONS: In short, this study confirmed and/or identified genetic, environmental and dietary risk factors associated with NPC susceptibility in a Southeast Asian population.
Influences of multiple genetic polymorphisms on ovarian cancer risk in Malaysia

Velapasamy S, Alex L, Chahil JK, Lye SH, Munretnam K, Hashim NA, et al.

Genet Test Mol Biomarkers, 2013 Jan;17(1):62-8.
PMID: 23113749 DOI: 10.1089/gtmb.2012.0223

The identification of high-risk individuals can help to improve early cancer detection and patient survival. Risk assessment, however, can only be accomplished if the risk factors are known. To date, the genetic risk factors for ovarian cancer, other than mutations in the BRCA1/2 genes, have never been systematically explored in Malaysia. The present study aims to identify from a panel of cancer-associated single-nucleotide polymorphisms (SNPs), those associated with ovarian cancer risk in Malaysia.
Fulltext Role of genetic & environment risk factors in the aetiology of colorectal cancer in Malaysia

Ramzi NH, Chahil JK, Lye SH, Munretnam K, Sahadevappa KI, Velapasamy S, et al.

Indian J Med Res, 2014 Jun;139(6):873-82.
PMID: 25109722

Colorectal cancer (CRC) is second only to breast cancer as the leading cause of cancer-related deaths in Malaysia. In the Asia-Pacific area, it is the highest emerging gastrointestinal cancer. The aim of this study was to identify single nucleotide polymorphisms (SNPs) and environmental factors associated with CRC risk in Malaysia from a panel of cancer associated SNPs.