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C K Heng

Publications and source records attributed to C K Heng.

At least 19 recordsLinked to original sources
PubMed2006

Spectral characterization of yeast cells with an epitaxy-based UV-Vis optical sensor.

The optical spectra of yeast cells in phosphate buffer saline (PBS) were analyzed with an optical UV-vis sensor based on a shallow p(+)n junction realized in a low doped n-type epitaxial silicon layer grown on a strongly doped n(+) substrate. The presence of the n/n(+) interface allows a significantly enhanced sensitivity, due to an increased collection of carriers photogenerated both by short and large wavelengths in the range 250...800 nm. In our experiments the optical absorption of yeast cells was investigated in the wavelength range 250...500 nm as a function of the cells concentration in PBS in the range of 6 x 10(6)-2 x 10(8) cells/ml. The main absorption peaks were found at 310, 350, 400 and 427 nm, respectively. A significant red shift of the wide absorption band at 427 nm has been observed when increasing cell concentration. This red shift behaviour was nonlinear, with saturation observed for yeast concentrations larger than 5 x 10(7) cells/ml. The half-peak bandwidth of this peak also showed a most significant nonlinear variation. These findings suggest that monitoring the parameters of the absorption band at 427 nm versus cells concentration could be used, e.g. using a dedicated integrated spectrometric microsystem, for fast quantitative measurements of yeast cell concentrations in various bio-samples, with possible applications in the food industry.

Biosensing Techniques↗
PubMed2006

The effects of three factor VII polymorphisms on factor VII coagulant levels in healthy Singaporean Chinese, Malay and Indian newborns.

Factor VII (FVII) is an independent risk factor for coronary artery disease. Three polymorphisms of the factor VII gene (F7) were studied in a group of healthy newborns comprising 561 Chinese, 398 Malays and 226 Asian Indians from Singapore. The allele frequencies of 3 polymorphisms (R353Q, Promoter 0/10bp Del/Ins and Intron 7) in the FVII gene were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments. In Chinese the minor allele frequencies are Q: 0.04, Ins: 0.03, R7: 0.44; Malays, Q: 0.06, Ins: 0.10, R7: 0.41; and Indians, Q: 0.25, Ins: 0.23, R7: 0.43. Strong linkage disequilibrium (Delta > 0.7) is observed between the 0/10 bp and the R353Q sites in all ethnic groups. We conclude that: (i) the prevalence of the minor Q and Ins alleles of the R353Q and 0/10 bp polymorphisms are significantly higher in the Indian newborns than the Chinese and Malays; (ii) the Q allele is significantly associated (p = 0.01) with a lower plasma FVII coagulant level in the Indian and Malay neonates; and this polymorphism explains up to 3.8% of the variance in FVII coagulant levels; (iii) there is no significant difference in allele frequencies of the three polymorphisms between neonates with and without family histories of CAD.

Antigens↗
PubMed2005

The association of mitochondrial DNA 5178 C > a polymorphism with plasma lipid levels among three ethnic groups.

Mitochondria are eukaryotic cytoplasmic organelles responsible for oxidative phosphorylation. The C to A nucleotide transversion in the NADH dehydrogenase subunit 2 (MT-ND2) coding region of mitochondrial DNA has been reported to be associated with plasma lipid levels, adult onset diseases and longevity. We have examined the role of this polymorphism in relation to plasma lipid levels and age in a total of 713 healthy individuals belonging to 3 ethnic groups in Singapore. The frequency of the A allele was significantly higher (p < 0.05) among the Chinese (0.15) in comparison to the Malays (0.05) and Indians (0.02). No significant difference in the frequency of the allele was observed between healthy and coronary artery disease subjects, and between age-stratified subjects. We found that the polymorphism is significantly associated in an ethnic- and gender-specific manner with plasma apoB levels in the Chinese males (p < 0.05). This is the first epidemiological report of the mt5178 C > A polymorphism and its association with plasma lipid levels in Asian populations outside Japan.

Adolescent↗
PubMed2003

Childhood nephrotic syndrome in relapse is associated with down-regulation of monocyte CD14 expression and lipopolysaccharide-induced tumour necrosis factor-alpha production.

Interleukin-13 (IL-13) is a known modulator of monocyte function, down-regulating monocyte surface markers such as CD14 and proinflammatory cytokines. We have shown previously that lymphocyte IL-13 gene expression was up-regulated during relapses in children with steroid-responsive nephrotic syndrome (SRNS). In this study, we examined the monocyte mRNA expression and lipopolysaccharide (LPS)-stimulated intracellular production of tumour necrosis factor-alpha (TNF-alpha) and IL-8 in children with SRNS during relapse and remission. Additionally, we investigated CD14 mRNA levels, CD14 surface expression and its soluble component (sCD14) in serum. Our results showed that the percentages of TNF-alpha positive monocytes following LPS stimulation were significantly lower in nephrotic children in relapse (64.4 +/- 13.7%) compared to remission (81.6 +/- 9.0%, P < 0.005). This was associated with down-regulation of CD14 mRNA, as well as both membrane and sCD14 in patients with nephrotic relapse (82.9 +/- 10.1% and 1.23 +/- 0.30 micro g/ml, respectively) compared to remission (93.9 +/- 3.2% and 1.77 +/- 0.82 micro g/ml, respectively) (P < 0.003). Although we demonstrated a decrease in LPS-stimulated intracellular production of TNF-alpha in monocytes from patients with nephrotic relapse, we were unable to show a concomitant decrease in mRNA expression during relapses. This could be explained by down-regulation of gene expression at the translational rather than transcriptional level. In conclusion, it is conceivable that up-regulation of T-cell IL-13 production in children with active nephrotic relapse was associated with suppression of monocyte CD14 expression, down-regulating pro-inflammatory cytokine production, and could account for the increased susceptibility to bacterial sepsis seen in nephrotic children in active relapse.

Adolescent↗
PubMed2003

Predicting risk of coronary artery disease from DNA microarray-based genotyping using neural networks and other statistical analysis tool.

This paper presents a novel approach for complex disease prediction that we have developed, exemplified by a study on risk of coronary artery disease (CAD). This multi-disciplinary approach straddles fields of microarray technology and genetics, neural networks (NN), data mining and machine learning, as well as traditional statistical analysis techniques, namely principal components analysis (PCA) and factor analysis (FA). A description of the biological background of the study is given, followed by a detailed description of how the problem has been modeled for analyses by neural networks and FA. A committee learning approach for NN has been used to improve generalization rates. We show that our NN approach is able to yield promising prediction results despite using only the most fundamental network structures. More interestingly, through the statistical analysis process, genes of similar biological functions have been clustered. In addition, a gene marker involved in breaking down lipids has been found to be the most correlated to CAD.

Algorithms↗
PubMed2002

Genotype associations of factor VII gene with plasma factor VII coagulant activity and antigen levels in healthy Chinese.

A raised plasma factor VII (FVII) level is one of the risk factors for coronary artery disease. The R353Q polymorphism at codon 353 and the 10 base pair (bp) insertion (0/10 bp) polymorphism of the FVII gene have been reported to be associated with plasma FVII levels in several populations. We investigated these two polymorphisms in 209 male and 214 female healthy Chinese. The allele frequencies of 10 bp and Q were 0.036 and 0.045, respectively. Strong linkage disequilibrium was observed between these two sites (Delta = 0.85, P < 0.001). There were significant genotype associations of these two loci with FVII coagulant activity (FVIIc) and antigen (FVIIAg) levels. Heterozygous individuals had lower FVIIc and FVIIAg levels than those homozygous for the common alleles. When analyzed separately by gender, the 0/10 bp polymorphism was strongly associated with FVIIAg levels in males and females. However, both polymorphisms were significantly associated with FVIIc levels only in the females. The effect of 0/10 bp polymorphism predominated over that of the R353Q polymorphism in a two-way analysis of variance procedure. In the Chinese, the 10 bp insertion may reduce transcription of the FVII gene, leading to the decreased synthesis of FVII protein and thus FVIIc.

Adult↗
PubMed2001

Risk factors for steroid dependency in children with idiopathic nephrotic syndrome.

Minimal change disease, the most common cause of idiopathic nephrotic syndrome (INS) in children, has a high relapse rate, with approximately half of patients developing steroid dependency. This study was aimed at determining the predictive risk factors for the development of steroid dependency in children diagnosed with INS. A retrospective study of 123 children with steroid-responsive INS, followed for at least 6 months between December 1974 and December 1999, was conducted. The following parameters were studied as predictors of steroid dependency: age at onset, gender, race, microscopic hematuria at onset, atopy, concomitant upper respiratory tract infections (URTI) during relapses, and days to remission with initial steroid therapy. Of the 91 children who fulfilled the inclusion criteria, 61.5% became steroid dependent. Both univariate and logistic regression analyses revealed that initial remission time of 9 or more days (P=0.02, OR=3.0, 95% CI=1.2-7.9) and concomitant URTI during relapses (P=0.01, OR=3.4, 95% CI=1.3-8.8) were significant predictors of steroid dependency. By identifying those children with predictive factors of steroid dependency, the clinician will be better able to plan the long-term management of these patients and reduce the morbidity seen with the frequent relapses and steroid treatment, in a disease that is otherwise associated with a favorable prognosis.

Child, Preschool↗
PubMed2001

Variations in the promoter region of the apolipoprotein A-1 gene influence plasma lipoprotein(a) levels in Asian Indian neonates from Singapore.

We studied the influence of two DNA polymorphisms (-75 bp G/A and +83 bp C/T) in the promoter region of the apolipoprotein A-1 (apoA1) gene on cord plasma level of lipoprotein(a) [Lp(a)] in 1076 newborns of both genders from the three major ethnic groups in Singapore-Chinese, Malays, and Asian Indians. The frequency of the A: allele at -75 bp in the Indians was significantly lower than the Chinese and Malays. There was no linkage disequilibrium between the two sites studied. Both polymorphic sites were not significantly associated with any lipid factors except for Lp(a) levels in the Asian Indians. The AA and CC homozygotes were significantly associated with lower Lp(a) levels. These associations were specific only to the male Indian neonates. The genetic variations at the -75 and +83 bp explained 6.9% and 7.2%, respectively, of the total variability of plasma Lp(a) levels at birth in the Asian Indians. The Lp(a) levels were also significantly different between composite genotypes in the order GG/TT > GA/CT > GG/CT > GA/CC > GG/CC > AA/CC. The effects of the two polymorphisms seem to be additive as the composite genotypes were able to explain 14% of the Lp(a) variance, equivalent to the sum of the two constituent sites. Our results showed that there is significant ethnic- and gender-specific influence of the apoA1 gene on plasma Lp(a) levels at birth that is inherent and independent of known gene-environment interactions.

Apolipoprotein A-I↗
PubMed2000

Cladistic analysis: its applications in association studies of complex diseases.

INTRODUCTION: With the increase in genotype data generated by high throughput typing technologies, there is currently a lack of complexity-oriented analytical methods that can maximise the information obtained from these raw data for the study of complex diseases. We introduce the cladistic analysis that is traditionally applied in evolution studies and taxonomy, to specify relevant comparisons of traits associated with each haplotype/genotype in a population sample. METHODS: Haplotypes are determined from the genotype data and linked to each other by their evolutionary relationships to form a cladogram. This is then used to specify relevant statistical comparisons. The central assumption is that any functionally important genetic variation causing a phenotypic effect at any point in the course of evolution will be embedded in the framework of haplotypes represented by the cladogram. APPLICATIONS: There are various applications of cladistic analysis in the study of complex diseases. Basically, it helps in the identification of haplotypes that are associated with a disease state or a significantly altered level of quantitative trait. However, its limitations are that only polymorphic sites on the same DNA strand can be analysed and that recombination events must be relatively rarer than mutational events. CONCLUSIONS: In the absence of methods that can recognise the complexity of the genotype organization, and given its ability to exploit evolutionary information for optimising the analytical strategy, cladistic analysis would be a method of choice for studying multi-loci effects on a quantitative trait or disease outcome.

Genetic Variation↗
PubMed1999

Evolution of the apolipoprotein B gene and coronary artery disease: a study in low and high risk Asians.

This study traces the evolutionary pathways of the apolipoprotein B gene in the low risk Chinese and high risk Asian Indians in relation to coronary artery disease (CAD). Haplotypes were constructed from six apoB polymorphisms sp24/27, Ag(c/g), Ag(a1/d), XbaI, Ag(h/i) and, Ag(t/z). These were genotyped from 474 Chinese (253 healthy, 221 CAD patients) and 248 Asian Indians (164 healthy, 84 CAD patients). The maximum parsimony method was used to construct a cladogram for each ethnic group. Three haplotypes in the Chinese and one in the Indians were found exclusively in CAD patients. These haplotypes were sp27ca1X-ht, sp24ga1X-iz and sp24ca1X + it in Chinese, and sp24cdX-it in Indians. Those in the Chinese all occurred as terminal haplotypes and represented the most recent mutations. Evolutionary pathways for both ethnic groups were similar for majority of the haplotypes except for the presence of an additional third branch in the Indians arising from the ancestral haplotype. However, this third branch does not appear to contribute to the susceptibility of the Indians to CAD.

Apolipoproteins B↗
PubMed1997

Plasma lipids and lipoprotein(a) levels in the Chinese from China and Singapore.

This study compared the influence of environmental factors on plasma lipid levels between the descendants of immigrant southern Han Chinese (Singapore Chinese, n = 275) and the native Chinese from southern China (n = 277). Their lipid profiles including lipoprotein (a) [Lp(a)] were measured and compared. The alpha level was set at 0.05 throughout the analysis. Body mass index (BMI), plasma total cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC) and triglycerides (TG) levels were significantly elevated in the Singapore Chinese. Plasma Lp(a) however, was comparable in both groups for concentrations as well as frequency distributions. Since both groups were genetically identical, the similar Lp(a) level was in agreement with studies which reported that the apolipoprotein(a) [apo(a)] gene explained as much as 70% of the plasma Lp(a) variations in Chinese. No correlation of plasma Lp(a) level was observed with age and BMI while significant positive linear correlations were observed with TC and LDLC in the male subjects only. We concluded that environmental factors (possibly affluent lifestyle and westernised diet) have significantly influenced the lipid risk factor levels of the Singapore Chinese whereas Lp(a) levels, which are predominantly under genetic control, were not altered significantly.

Adult↗
PubMed1997

Genotype associations among seven apolipoprotein B polymorphisms in a population of Orang Asli of western Malaysia.

Associations among seven apolipoprotein B (APOB) gene polymorphisms [C-T promoter site; Leu-Ala-Leu signal peptide (SP) insertion/deletion; AG C,G site at codon 71; AG A1,D site at codon 591; XbaI site at codon 2488; AG H,I site at codon 3611; and AG T,Z site at codon 4154] were investigated in 195 members of an Orang Asli (aborigine) population from western Malaysia. Frequencies of the rare alleles for all these polymorphisms turned out to be low when compared with European but not Asian populations. The AG H,I site was not polymorphic. The highly polymorphic sites are in linkage disequilibrium among themselves, as shown by their delta values: SP 24,27 and AG C,G, 0.68; SP 24,27 and AG A1,D, 0.71; XbaI and AG C,G, 0.64; XbaI and AG A1,D, 0.57; SP 24,27 and XbaI, 0.48; and AG C,G and AG A1,D, 0.68. Ten unequivocal haplotypes on the basis of six sites (excluding the promoter polymorphism) were observed, and they represent 80% of the sample. The frequency of haplotype SP27,G,A1,X-,I,T, defined by the common homozygotes at all the sites for the APOB gene was 0.7, compared with 0.22 in Europeans. The ancestral haplotype SP27,G,D,X-,I,T was present at low frequency (0.01) in both the Orang Asli and Europeans. A cladogram constructed on the basis of haplotypes in the Orang Asli shows two different lines of evolution and that other haplotypes evolved by subsequent mutations on the ancestral haplotype.

Apolipoproteins B↗
PubMed1996

Racial variation of cord plasma lipoprotein(a) levels in relation to coronary risk level: a study in three ethnic groups in Singapore.

Lipoprotein(a) [Lp(a)] is recognized as an independent risk factor for atherosclerosis. Studies have also shown that there are racial differences in the Lp(a) profile. The multiracial population of Singapore has demonstrated a differential prevalence of coronary artery disease, which is concordant with the plasma Lp(a) profile in the adult populations of Singapore. The level of Lp(a) is under strict genetic control, and its plasma concentration is determined significantly by inheritance. Expression of the racial profile of Lp(a) at birth was studied in the cord blood of 542 male and 468 female newborns from three ethnic groups of Singapore using the sandwich-ELISA. The Lp(a) levels were then related to the coronary risk levels of their respective adult populations. Lp(a) levels in Singapore newborns were found to be independent of the infant's birth weight and sex but were significantly influenced by race. Indian newborns had significantly higher plasma levels of Lp(a). Chinese newborns had the lowest Lp(a) levels at birth. The ranking of Lp(a) levels at birth was concordant with the relative coronary mortality rates for the respective adult populations of Singapore. Racial differences in plasma Lp(a) levels are present and expressed at birth.

Analysis of Variance↗
PubMed1995

Racial variation of factor VII activity and antigen levels and their correlates in healthy Chinese and Indians at low and high risk for coronary artery disease.

Plasma factor VII activity (FVIIc) is one of the independent risk factors of coronary artery disease (CAD) and is controlled by both genetic and environmental factors. South Asians including Indians have one of the highest prevalence and mortality rates from CAD while the Chinese have a much lower risk. Generally accepted risk factors cannot explain the high mortality from CAD in Indians. We examined two hundred and seventy seven Chinese (124 m, 153 f); and 216 healthy Indian (150 m, 66 f) adults for serum lipids; plasma FVIIc and FVIIag levels in order to examine racial variations of these and their correlates in these two populations. Both Indian men and women had significantly higher FVIIc levels (12% and 11%, respectively) than the Chinese even after adjustments of age, BMI and lipids (P < 0.01). In contrast, Indians had significantly lower plasma FVIIag levels than Chinese (8% and 9%, respectively in men and women; P < 0.01). Multiple linear regression analysis shows a strong correlation of FVIIc with serum triglycerides accounting for 4-8% of the total variability of FVIIc in different groups. Further, there was a stronger correlation between FVIIc and FVIIag in Indians than that in the Chinese (0.43 vs. 25) suggesting a greater activation resulting in higher FVIIc in Indians inspite of lower FVIIag levels. The higher FVIIc and stronger activation by triglycerides observed in this study partly explain the higher risk of CAD in Indians.

Adult↗