OBJECTIVE: The goal of this study was to determine the frequencies of SNPs rs1042114, rs702764, rs1997794, rs1022563 and rs910080 in the Malaysian population and to study their association with opioid dependence in Malaysian Malays.
METHODS: A total of 459 Malay male with opioid dependence and 543 healthy male (controls) subjects were included in this study. SNPs were genotyped using the TaqMan SNP genotyping assay. Statistical analysis was performed using Golden Helix SVS software suite to identify the distribution of allele and genotype frequencies, and SNP-SNP interactions were also analysed in this study.
RESULTS AND DISCUSSION: SNP rs1042114 in the OPRD1 gene is strongly associated with opiate addiction (P=.0001). In individuals homozygous for this risk allele, the likelihood of opiate addiction is increased by a factor 1.62 (95% confidence interval (CI) 1.412-1.875). Polymorphic alleles at SNP rs702764 of OPRK1 were not associated with opioid dependence. A significant association between opioid dependence and SNP rs910080 of PDYN (P=.0217) was detected, but there was no association for SNPs rs199774 and rs1022563. A significant interaction was also identified between homozygous wild-type genotype TT of rs702764 with the risk genotypes TG/GG of rs1042114 (odds ratio (OR)=2.111 (95% CI 1.227-3.631), P=.0069) and with the risk genotypes GA/AA of rs910080 (OR=1.415 (95% CI 1.04-1.912), P=.0239).
WHAT IS NEW AND CONCLUSION: The results indicate that SNPs rs1042114 and rs910080 contribute to vulnerability to opioid dependence in the Malaysian Malay population. These results will help us to understand the effect of the SNPs and the SNP-SNP interaction on opioid dependence and may assist in efforts to screen vulnerable individuals and match them with individually tailored prevention and treatment strategies.
METHODS: Two-hundred unrelated Emirati parents of patients selected for bone marrow transplantation were genotyped for HLA class I (A, B, C) and class II (DRB1, DQB1) genes using reverse sequence specific oligonucleotide bead-based multiplexing. HLA haplotypes were assigned with certainty by segregation (pedigree) analysis, and haplotype frequencies were obtained by direct counting. HLA class I and class II frequencies in Emiratis were compared to data from other populations using standard genetic distances (SGD), Neighbor-Joining (NJ) phylogenetic dendrograms, and correspondence analysis.
RESULTS: The studied HLA loci were in Hardy-Weinberg Equilibrium. We identified 17 HLA-A, 28 HLA-B, 14 HLA-C, 13 HLA-DRB1, and 5 HLA-DQB1 alleles, of which HLA-A*02 (22.2%), -B*51 (19.5%), -C*07 (20.0%), -DRB1*03 (22.2%), and -DQB1*02 (32.8%) were the most frequent allele lineages. DRB1*03~DQB1*02 (21.2%), DRB1*16~DQB1*05 (17.3%), B*35~C*04 (11.7%), B*08~DRB1*03 (9.7%), A*02~B*51 (7.5%), and A*26~C*07~B*08~DRB1*03~DQB1*02 (4.2%) were the most frequent two- and five-locus HLA haplotypes. Correspondence analysis and dendrograms showed that Emiratis were clustered with the Arabian Peninsula populations (Saudis, Omanis and Kuwaitis), West Mediterranean populations (North Africans, Iberians) and Pakistanis, but were distant from East Mediterranean (Turks, Albanians, Greek), Levantine (Syrians, Palestinians, Lebanese), Iranian, Iraqi Kurdish, and Sub-Saharan populations.
CONCLUSIONS: Emiratis were closely related to Arabian Peninsula populations, West Mediterranean populations and Pakistanis. However, the contribution of East Mediterranean, Levantine Arab, Iranian, and Sub-Saharan populations to the Emiratis' gene pool appears to be minor.
MATERIALS AND METHODS: A total of 195 Thin Prep Pap smear samples from HPV negative and cancer free females were randomly selected as controls while 106 formalin fixed paraffin embedded samples from females with invasive cervical cancer were randomly selected for the cases group. The polymorphisms were identified using restriction fragment length polymorphism (RFLP) PCR.
RESULTS: We found no significant associations between CYP1A1 MspI polymorphism and cervical cancer in the general Malaysian female population. However, upon ethnic stratification, the variant C/C genotype was significantly associated with a 4.66-fold increase in cervical cancer risk in Malay females (95% CI= 1.21-17.9; p=0.03). No significant association was observed in the Chinese and Indian females. Additionally, there were no significant associations in the dominant model and allele frequency model analysis in both the general and ethnically stratified female population of Malaysia.
CONCLUSIONS: Our findings suggest that the C/C genotype of CYP1A1 MspI polymorphism is associated with the development of cervical carcinoma in the Malay females of Malaysia.
METHODS: Articles that report genetic polymorphisms, genotype frequencies and allele frequencies in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 were retrieved from the PubMed database.
RESULTS AND DISCUSSIONS: A total of 86 studies that fulfilled the eligibility criteria representing different ethnic populations of SEEA, ie, Burmese, Chinese, Japanese, Karen ethnic minority, Korean, Malaysian, Philippino, Singaporean, Taiwanese, Thai, Indonesian, and Vietnamese, were included in the analysis. In general, the genotype frequencies across SEEA populations are comparable. The CYP2C9*1/*1 (69.3%-99.1%), *1/*3 (2.3%-20.1%) and *3/*3 (0%-2.2%) genotypes are reported in most SEEA populations. Six major CYP2C19 genotypes, ie, *1/*1 (6.25%-88.07%), *1/*2 (21.5%-86.46%), *1/*3 (0.8%-15.8%), *2/*2 (3.4%-14.5%), *2/*3 (0%-7.3%) and *3/*3 (0%-10.2%), are reported in most SEEA populations. Major CYP2D6 genotypes include *10/*10 (0%-69.6%), *1/*1 (0%-61.21%) and *1/*10 (0%-62.0%). Major CYP3A5 genotypes are *3/*3 (2.0%-71.4%), *1/*3 (16.0%-57.1%) and *1/*1 (0%-82.0%). Genotyping of abnormal genotypes of CYP2C9 (*1/*3), CYP2C19 (*1/*2, *1/*3), CYP3A5 (*1/*3) and CYP2D6 (*5/*10) associated with IM (Intermediate metabolizer) status, may be clinically beneficial in SEEA populations. Similarly, with CYP2C19 (*2/*2, *2/*3), CYP2D6 (*5/*5 ) linked to PM (Poor metabolizer), CYP2D6 (*10/*10, *1/*5 and to lesser extent *1/*4, *2/*5, *10/*41, *10/*49, *10/*14) and CYP3A5 (*1/*1) associated with EM (extensive metabolizer).
WHAT IS NEW AND CONCLUSION: Sufficient number of studies has provided comparable results in general. This review suggests that comparable genotype frequencies of CYP2C9, CYP2C19, CYP2D6 and CYP3A5 exist among the SEEA populations. It is noted that more research data are reported from East Asians compared with South-East Asians. Concerned efforts are required to establish partnerships among SEEA countries that will ensure sufficient data from South-East Asian countries which will assist in establishing the databases for SEEA populations.