J. S. H. Tay

Influence of serum paraoxonase polymorphism on serum lipids and apolipoproteins.

One hundred and sixty‐three healthy Chinese subjects of both sexes were studied for serum paraoxonase (PON) polymorphism, and levels of lipids and apolipoproteins in order to examine effects of PON alleles on these parameters. The level of serum triglyceride was significantly higher in high activity allele (PON*B) compared with that in low activity allele (PON*A) in both sexes (P<0.01). The subjects with PON A had significantly higher LDL cholesterol (P<0.05) and lower Apo A‐II and ApoB levels. The influence of serum paraoxonase on serum lipids was estimated further by Spearmans rank correlation. In the males, there was a significant negative correlation of serum paraoxonase activity with total (P<0.05) and LDL (P<0.01) cholesterol levels, and positive correlation with HDL cholesterol and Apo A‐II levels (P< 0.05). Serum paraoxonase activity had a high positive correlation with serum triglyceride levels in both sexes (P< 0.001). Serum ApoB level had a positive correlation with the enzyme activity only in females (P<0.01). The allelic effect of PON on these parameters was studied by multiple regression analysis. The high activity allele (PON*B) was associated with higher serum triglyceride level (P<0.001) and ApoB (P<0.001), while it had lowering influence on total cholesterol (P<0.05) and LDL cholesterol (P<0.005) in men. The average allelic effect of PON was found to be about 22% for serum triglycerides, 11% for LDL cholesterol, 14% for Apo A‐II and 19% for Apo B in the present study. This study suggests a possible significant role of serum paraoxonase alleles in the metabolism of serum lipids and apolipoproteins.

DNA polymorphisms of the apolipoprotein B gene are associated with obesity and serum lipids in healthy Indians in Singapore

Saha N, Tay JSH, Heng CK, Humphries SE. DNA polymorphisms of the apolipoprotein B gene are associated with obesity and serum lipids in healthy Indians in Singapore.

Lack of association of angiotensin-converting enzyme (ACE). Gene insertion/deletion polymorphism with CAD in two Asian populations

Association of the insertion/deletion polymorphism of the angiotensin‐converting enzyme (ACE) gene with coronary artery disease with or without myocardial infarction (MI) was examined in a group of Chinese and Indian men in Singapore. The sample comprised an angiographically confirmed patient group of 276 Chinese and 102 Indians, of which 155 Chinese and 72 Indians had MI, and a matched healthy control group (147 Chinese and 166 Indians). The frequency of the D allele in the Chinese was 0.39 in those with CAD with MI, 0.43 in those with CAD but without MI, and 0.41 in the control group. The frequency of the D allele in Indians was 0.44 in CAD with or without MI, and 0.45 in the control group. There was no significant association of the ACE gene with CAD or MI in the Chinese or Indians, either in the entire sample or in different risk groups. The frequency of the D allele was significantly lower in the healthy Chinese and Indians than that reported in Caucasians. The association of the ACE gene with MI or CAD observed in other studies could not be confirmed in the present series of Chinese and Indians in Singapore.

DNA polymorphisms of the apolipoprotein B gene in Chinese coronary artery disease patients

Five restriction fragment length polymorphisms (RFLP) of the apo B gene and their association with serum lipids and apolipoprotein levels have been studied in 139 Chinese patients with angiographically confirmed CAD (mean age 56.2 ± 0.8 years) and 154 healthy Chinese subjects (mean age 44.0 ± 1.0 years) of both sexes. The patient group had significantly higher levels of serum total and LDL cholesterol; and apo B (P<0.001) and lower HDL cholesterol and apo A‐I (P<0.001 and <0.01, respectively). The frequencies of the rarer alleles of the ins/del, XbaI and EcoRI (but not the PvuII and MspI) polymorphisms were significantly lower in the Chinese compared to those reported in Caucasians. There was no significant difference in allelic frequencies of the signal peptide region (Ins/Del), XbaI, MspI and EcoRI sites of the apo B gene between the patient and control groups. The frequency of the rarer allele of the PvuII RFLP was significantly lower in the CAD patients (P<0.05) compared to that in the control group (0.05 vs 0.10). None of the DNA polymorphisms was associated with a significant influence on serum lipid and apolipoprotein levels in the patients with coronary artery disease.

Molecular variants of red cell glucose-6-phosphate dehydrogenase deficiency in Central Java, Indonesia

One hundred and sixty-nine Javanese males were screened for the presence of red cell glucose-6-phosphate dehydrogenase (G6PD) variants by a dye decoloration screening test and starch gel electrophoresis. The frequency of G6PD deficiency was 14%. Three non-deficient electrophoretic variants with mobilities of 95, 105 and 107% of GdB+ were encountered. Sixteen G6PD-deficient subjects were further investigated for the presence of mutations at nt95 A-->G, nt487 G-->A, nt493 A-->G, nt563 C-->T, nt1024 C-->T, nt1376 G-->T, nt1388 G-->A and the silent mutation (nt1311 C-->T) of the G6PD gene by natural or artificially created amplified restriction sites. They were identified by the polymerase chain reaction and electrophoresis of restriction-digested products. Five subjects had the Mediterranean mutation (nt563 C-->T), but only one had simultaneous presence of nt1311(T). The next common mutations were 1376(T) in three subjects and 487(A) in two subjects. Five of the sixteen subjects had the nt1311(T) mutation giving an overall frequency of 0.31. The other four mutations were absent in this population sample.

Lack of association of apolipoprotein E polymorphism with plasma Lp(a) levels in the Chinese

Apolipoprotein E (apoE) polymorphism and its influence on plasma lipids, lipoproteins, lipoprotein (a) [Lp(a)] and apolipoproteins was studied in 536 (270 males and 266 females) healthy Chinese in Singapore. From analysis of variance with age and BMI as covariates, apoE genotype was found to exert a significant influence on plasma total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C) and apoB in females. Its effect in males was marginally significant only on LDL‐C. In both sexes, plasma TC, LDL‐C and apoB were lower in those who were E2‐3 than in those who were E3‐3. There was no significant difference in log‐transformed Lp(a) level between the apoE genotypes after adjusting for the confounding effect of LDL‐C in addition to age and BMI. The percentage variance (R2times100) of the lipid traits explained by apoE polymorphism in the females was 4.94% for plasma TC, 5.85% for LDL‐C and 4.25% for apoB. We conclude that: 1) ε2 allele had a lowering effect on plasma TC, LDL‐C and apoB; 2) apoE polymorphism did not have any significant influence on Lp(a) concentration; and 3) the effect of apoE polymorphism on plasma TC, LDL‐C and apoB was gender‐specific, with a stronger influence in females than in males.

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.

Molecular characterisation of red cell glucose-6-phosphate dehydrogenase deficiency in north-west Pakistan.

233 Pushtoons (129 males and 104 females), 51 Punjabi Muslims (29 males and 22 females) and 21 Afghans (15 males and 6 females) were screened for the presence of red cell glucose-6-phosphate dehydrogenase (G6PD) variants by a dye decolouration screening test and starch gel electrophoresis. The overall frequency of G6PD deficiency in males was found to be about 10%. 17 male G6PD-deficient samples were further investigated for the C-->T substitution at nucleotide (nt) 563 (the Mediterranean mutation) and the C-->T substitution at nt 1311 (the silent allele) of the G6PD gene by PCR amplification followed by digestion with appropriate restriction enzymes. 10 of the 13 Pushtoon, 2 Punjabi and 1 Afghan males had the 563 mutations. Only 1 (Punjabi) out of 13 G6PD-deficient males with the 563 mutation had the silent mutation at nt 1311. The frequency of the silent mutation was found to be about 0.20 in the 60 Pushtoon and 19 Punjabi non-deficient males.

Emotional and social effects of congenital heart disease in Singapore.

A cohort of patients with congenital heart disease (n=29) who had undergone corrective cardiac surgery was studied and compared with normal controls. The mean age of cardiac patients was 10.3 years with a range of 6 years to 16 years. Their emotional maladjustment as measured on a behavioural checklist was significantly higher (P < 0.01) than controls, and their social adjustment was also similarly less satisfactory (P < 0.05). Regression analysis indicated that emotional maladjustment in the child was related to maternal maladjustment (P < 0.01), maternal guilt (P < 0.01) and maternal anxiety (P < 0.05). Social maladjustment in the child was significantly related to maternal guilt (P < 0.05) and pampering (P < 0.02). It was considered that the child with heart disease was perceived and ‘labelled’ by the mother as abnormal even after surgery and was therefore the object and focus of maternal guilt and anxiety. Hence, the childs emotional and social maladjustment is probably the result of maternal factors rather than the physical handicaps of the illness.

Inflammatory response in bacterial meningitis: cytokine levels in the cerebrospinal fluid.

Inflammatory response plays an important role in the pathogenesis of cerebral injury in bacterial meningitis. In this study, we evaluated the cytokine levels of interleukin 1-beta (IL1 beta), tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL6) in the cerebrospinal fluid (CSF), and determined their correlation with acute clinical complications and with changes in CSF biochemistry. Interleukin 6, TNF alpha and IL1 beta were present in 9/9, 3/9 and 4/9 patients, respectively. The CSFs with detectable TNF alpha or IL1 beta had higher levels of IL6 (p < 0.02), protein (NS) and lower glucose levels (p < 0.02), compared with those in which TNF alpha and IL1 beta were absent. Tumour necrosis factor alpha and IL1 beta levels also correlated with the presence of prolonged fever, fits, spasticity and death (logTNF alpha: r = 0.70, p < 0.05; logIL1 beta: r = 0.62, p = 0.08). The cytokine levels reflect the degree of inflammatory response and are positively correlated with the severity of acute clinical complications. Modulation of this inflammatory response in bacterial meningitis may improve its morbidity and mortality.