ABSTRACT
BACKGROUND: A strong association has been documented between HLA-B*15:02 and carbamazepine-induced severe cutaneous adverse reactions (SCARs) in Asians. Human leucocyte antigen testing is potentially valuable in many countries to facilitate early recognition of patient susceptibility to SCARs. OBJECTIVES: To determine the cost-effectiveness of universal HLA-B*15:02 screening in preventing carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in an ethnically diverse Malaysian population. METHODS: A hybrid model of a decision tree and Markov model was developed to evaluate three strategies for treating newly diagnosed epilepsy among adults: (i) carbamazepine initiation without HLA-B*15:02 screening (current practice); (ii) universal HLA-B*15:02 screening prior to carbamazepine initiation; and (iii) alternative treatment [sodium valproate (VPA)] prescribing without HLA-B*15:02 screening. Base-case analysis and sensitivity analyses were performed over a lifetime time horizon. Incremental cost-effectiveness ratios were calculated. RESULTS: Both universal HLA-B*15:02 screening and VPA prescribing were dominated by current practice. Compared with current practice, universal HLA-B*15:02 screening resulted in a loss of 0·0255 quality-adjusted life years (QALYs) at an additional cost of 707 U.S. dollars (USD); VPA prescribing resulted in a loss of 0·2622 QALYs at an additional cost of USD 4127, owing to estimated differences in antiepileptic treatment efficacy. CONCLUSIONS: Universal HLA-B*15:02 screening is unlikely to be a cost-effective intervention in Malaysia. However, with the emergence of an ethnically diverse population in many other countries, this may render HLA-B*15:02 screening a viable intervention when an increasing proportion of the population is at risk and an equally effective yet safer antiepileptic drug is available.
Subject(s)
Anticonvulsants/adverse effects , Carbamazepine/adverse effects , HLA-B15 Antigen/metabolism , Stevens-Johnson Syndrome/prevention & control , Adolescent , Adult , Asian People/ethnology , Cost-Benefit Analysis , Efficiency , Epilepsy/drug therapy , Epilepsy/ethnology , Humans , Malaysia/ethnology , Markov Chains , Mass Screening/economics , Middle Aged , Quality-Adjusted Life Years , Stevens-Johnson Syndrome/economics , Stevens-Johnson Syndrome/ethnology , Young AdultABSTRACT
OBJECTIVE: Preterm birth (PTB) is a multifactorial complication in which genetic and environmental factors contribute to the phenotype. The AKAP10 protein encoded by AKAP10 gene has a vital role in the maintenance of myometrial quiescence and pregnancy. This study aimed to investigate whether polymorphisms in the AKAP10 gene are associated with the risk of PTB. STUDY DESIGN: A total of 664 women (132 preterm and 532 term) with spontaneous singleton deliveries were genotyped for AKAP10 polymorphisms (rs119672, rs203462 and rs169412) using Sequenom MassARRAY platform. RESULT: A significant association was observed between the CC and AC genotypes of AKAP10 rs169412 with reduced risk of PTB (CC: adjusted odds ratio (OR) 2.95, 95% confidence interval (CI): 1.23-7.09, P=0.016. AC: adjusted OR 3.46, 95% CI: 1.38-8.68, P=0.008), respectively. Following stratification by ethnicity, a significant association was observed between the AC and CC genotypes of rs169412 and term birth in the Malay ethnic subgroup. (CC: OR 2.9, 95% CI: 1.01-8.59, P=0.041. AC: OR 3.14, 95% CI: 1.04-9.54, P=0.043). A significant association was also observed between the CT genotypes of AKAP10 rs119672 with reduced risk of PTB deliveries (CT: OR 3.2, 95% CI: 1.06-9.76 P=0.007, TT: OR 2.8, 0.98-8.34, P =.0.015) Alternatively, there was no association between AKAP10 rs169412 and rs119672 polymorphisms with PTB in the Indians and Chinese ethnic groups. CONCLUSION: This study indicates a significant association between the AKAP10 polymorphisms and reduced risk of PTB in the Malays. This demonstrates the potential role of AKAP10 polymorphisms in preterm complications.
Subject(s)
A Kinase Anchor Proteins/genetics , Premature Birth , Adult , Ethnicity/genetics , Female , Humans , Malaysia/epidemiology , Polymorphism, Single Nucleotide , Pregnancy , Premature Birth/ethnology , Premature Birth/geneticsABSTRACT
A genome-wide association study showed that the tagging single nucleotide polymorphism (SNP) rs7566605 in the insulin-induced gene 2 (INSIG2) was associated with obesity. Attempts to replicate this result in different populations have produced inconsistent findings. We aimed to study the association between the rs7566605 SNP with obesity and other metabolic parameters in Malaysian Malays. Anthropometric and obesity-related metabolic parameters and DNA samples were collected. We genotyped the rs7566605 polymorphism in 672 subjects using real-time polymerase chain reaction. No significant associations were found between the rs7566605 tagging SNP of INSIG2 with obesity or other metabolic parameters in the Malaysian Malay population. The INSIG2 rs7566605 SNP may not play a role in the development of obesity-related metabolic traits in Malaysian Malays.
Subject(s)
Intracellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Obesity/ethnology , Obesity/genetics , Polymorphism, Single Nucleotide , Adult , Body Mass Index , Female , Gene Expression , Genome-Wide Association Study , Genotype , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Malaysia/epidemiology , Male , Membrane Proteins/metabolism , Middle Aged , Obesity/metabolism , PhenotypeABSTRACT
The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D’ = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.
Subject(s)
Female , Humans , Male , Middle Aged , Genetic Predisposition to Disease/genetics , Linkage Disequilibrium/genetics , Obesity/genetics , Polymorphism, Single Nucleotide/genetics , Proteins/genetics , Body Mass Index , Case-Control Studies , Genotype , Malaysia/ethnology , Obesity/ethnologyABSTRACT
The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D' = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.
