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Biomedical subjects

G N Thomas

Publications and source records attributed to G N Thomas.

32 records · Page 2Linked to original sources
PubMed2000

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene and obesity in Chinese subjects with components of the metabolic syndrome.

BACKGROUND: In regions such as Hong Kong, rapid economic development has led to lifestyle alterations characterized by increases in energy and fat intake and reduction in physical activity. These changes have been associated with a dramatic increase in the prevalence of diabetes and related diseases of the metabolic syndrome. OBJECTIVE: To investigate if a common polymorphism (Trp64Arg) of the beta3-adrenergic receptor gene, previously implicated as predisposing to type 2 diabetes mellitus or obesity in other populations, has a role in the apparent susceptibility of Hong Kong Chinese to diabetes and related disorders. METHOD: A PCR-based protocol was used to genotype 802 Southern Chinese subjects who were either healthy or had one or more of the metabolic disorders including diabetes, hypertension or dyslipidaemia. RESULTS: The frequencies of the mutant A allele (12.7%) and AA genotype (1.7%) did not differ, by the chi2 test, in any patient group with diabetes, hypertension or dyslipidaemia, alone or in combination, compared to healthy controls. Using the t-test in the 802 subjects, those carrying the mutant A allele had evidence of increased obesity with a significantly (all P<0.05) higher body mass index (BMI, kg/m2) and also lower HDL-cholesterol. BMI was also elevated in subjects with the A allele in the separate groups with diabetes, dyslipidaemia or hypertension. Stepwise multiple regression showed this polymorphism to be an independent predictor of BMI. CONCLUSION: These data do not support any direct involvement of the Trp64Arg polymorphism in the development of diabetes, hypertension or dyslipidaemia in Chinese subjects, but do suggest a relationship with obesity.

Adult↗
PubMed2000

Obesity, independent of insulin resistance, is a major determinant of blood pressure in normoglycemic Hong Kong Chinese.

Obesity and insulin resistance are considered important links underlying the development of hypertension. In Caucasians, there have been many reports of an association between insulin resistance and hypertension. However, this relationship is not consistently found in other ethnic groups. In this study, we examined the involvement of insulin resistance (assessed as fasting insulin-glucose product, FIGP) and general and central obesity as potential links in the development of hypertension in 413 normoglycemic Hong Kong Chinese (56.9% hypertensive) subjects. Anthropometric parameters (waist circumference [WC], waist-to-hip ratio [WHR], body mass index [BMI]), surrogate measures of insulin resistance (fasting plasma glucose, insulin, FIGP), fasting lipids and systolic (SBP) and diastolic (DBP) blood pressure were measured. Both male and female hypertensives were more obese and dyslipidemic, and the females had higher indices of insulin resistance than the normotensive subjects of the same gender. Before adjustment for age, gender, and adiposity, FIGP correlated with SBP in the total (r = .19, P = .009) and low BMI (r = .23, P < .05) and low WHR (r = .25, P < .01) groups. However, after adjustment, there was no significant relationship between FIGP and blood pressure. In contrast, BMI and WC were strongly associated with blood pressure (r > or = .41, P < .001 for both DBP and SBP in the total population), although in the group with general obesity, the strength of the relationship was weaker (r > or = .13). These relationships persisted after adjustment for age, gender, and FIGP. Obesity, therefore, appears to have a predominant role compared with insulin resistance in determining blood pressure in these normoglycemic Chinese.

Adult↗
PubMed2000

Tumor necrosis factor alpha gene G-308A polymorphism in the metabolic syndrome.

Tumor necrosis factor alpha (TNF-alpha) is a multifunctional cytokine constitutively produced by adipose tissue that may mediate insulin resistance. Studies in Caucasian subjects have suggested that the G-308A transition in the 5' region of the TNF-alpha gene may be associated with insulin resistance and obesity. These factors have been proposed to underlie the clustering of type 2 diabetes, hypertension, and dyslipidemia found in the metabolic syndrome, the prevalence of which is reaching epidemic proportions in Hong Kong Chinese. We investigated the association of this gene polymorphism with the components of the metabolic syndrome including the lipid profile, as well as with the indices of obesity and insulin resistance as measured by the insulin-glucose product, in 440 Chinese subjects (healthy [27.5%] and overlapping groups with type 2 diabetes [54.1%], hypertension [38.8%], dyslipidemia [39.3%], or obesity [39.5%]). The frequency of the mutant A allele was 7.4% in 121 healthy controls and 9.0% in the total population. The mutation was not associated with any component of the metabolic syndrome or with the prevalence of albuminuria and retinopathy in these subjects. Furthermore, there was no difference in anthropometric measures, insulin resistance, or lipid levels between subjects with the GG genotype and those with the mutant allele. In summary, the TNF-alpha gene G-308A polymorphism is unlikely to play an important role in the development of these disorders in this population.

Diabetes Mellitus, Type 2↗
PubMed2000

Renin-angiotensin-aldosterone system gene polymorphisms and hypertension in Hong Kong Chinese.

In Chinese populations, hypertension is common and is a major risk factor for cerebrovascular and coronary heart disease. The renin-angiotensin-aldosterone system (RAAS) helps maintain blood pressure and salt homeostasis and appears important in the pathogenesis of hypertension and some forms of vascular disease. We investigated three RAAS gene polymorphisms, the angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T and angiotensin II type 1 receptor A1166C polymorphisms in 232 hypertensive and 178 normotensive Chinese subjects. The hypertensives were generally more obese and dyslipidaemic. No significant differences in genotype or allele frequencies for any of the polymorphisms were identified between the groups, nor was there any interactive contribution to blood pressure by the ACE and AGT polymorphisms. However, there were large differences in genotype and allele frequencies between the healthy Chinese and published data for equivalent Caucasian populations. These findings suggest these polymorphisms are unlikely to be involved in the pathogenesis of hypertension in Chinese.

Adult↗
PubMed2000

Modulation of blood pressure and obesity with the dopamine D2 receptor gene TaqI polymorphism.

Pharmacological data suggest that obesity and blood pressure (BP) may be modulated through the dopamine D2 receptor (DD2R), which may represent an underlying mechanism that links these conditions. A TAQ:I polymorphism near the DD2R gene has been associated with indices of obesity in white populations. We compared anthropometric and fasting plasma biochemical parameters between 209 nondiabetic hypertensive and 174 gender-matched normotensive Chinese subjects. The hypertensives had increased dyslipidemia, increased fasting plasma glucose concentrations, and a greater degree of obesity. The A1 and A2 alleles of the DD2R gene TAQ:I polymorphism were identified with a polymerase chain reaction-based restriction fragment length polymorphism protocol. The A1 allele frequency was decreased in the hypertensives (42.0%) compared with the control subjects (52.0%, P=0.006), and genotype frequencies were different (P=0.05) between the 2 groups. In the combined population (n=383), systolic, diastolic, and mean arterial BPs were 6, 5, and 6 mm Hg lower, respectively, in subjects with the A1A1 genotype relative to the A2A2 genotype (all P<0.05), whereas skinfold thickness was increased at the iliac (P<0.001) and triceps (P<0.03) sites but not at the biceps or subscapular sites. Furthermore, this DD2R gene polymorphism was shown to be a significant independent predictor of diastolic BP and iliac and triceps skinfold thicknesses (all P<0.03). These contrasting associations of the DD2R TAQ:I polymorphism A1 allele with lower BP but increased markers of "gynoidal" or peripheral subcutaneous obesity (iliac and triceps skinfold thicknesses) in our Chinese population may provide some insight into the underlying relationship between BP and body fat distribution, but the exact nature of this link remains to be determined.

Adult↗
PubMed2000

Obesity is the key determinant of cardiovascular risk factors in the Hong Kong Chinese population: cross-sectional clinic-based study.

OBJECTIVES: To examine the interrelationships between obesity and various cardiovascular risk factors, and to investigate the relative importance of insulin and obesity in their associations with various pathophysiologies. DESIGN: Cross-sectional clinic-based study. SETTING: Medical clinics at a university teaching hospital, Shatin, Hong Kong. PARTICIPANTS: A heterogeneous cohort of 767 Hong Kong Chinese subjects with a mean age of 43 (standard deviation, 14) years. MAIN OUTCOME MEASURES: Body mass index, waist circumference, plasma insulin, insulin resistance index, fasting plasma glucose and lipid levels, blood pressure, and 24-hour urinary albumin excretion. RESULTS: Pathophysiological abnormalities and risk factors are frequently clustered to varying degrees. Compared with the control subjects, patients with at least one component of the metabolic syndrome were more obese, hyperinsulinaemic, insulin resistant, hyperglycaemic, hypertensive, dyslipidaemic, and albuminuric (all variables, P<0.001). Increasing degrees of body mass index, waist circumference, plasma insulin level, and insulin resistance index were associated with an increasing number of risk factors after adjusting for age and sex (all variables, P<0.02). Multiple regression analysis showed that obesity, as reflected by either the body mass index or waist circumference, had a closer association than plasma insulin with the fasting plasma glucose concentration, blood pressure, and high-density lipoprotein-cholesterol and triglyceride concentrations. Using 19.0-20.9 kg/m(2) as the reference body mass index interval, the lowest cardiovascular risk was associated with a body mass index of <23.0 kg/m(2). There was an increased risk of 3.1 and 5 times when the body mass index was 23. 0-24.9 kg/m(2) and > or =25 kg/m(2), respectively. CONCLUSIONS: Obesity, hyperinsulinaemia, and insulin resistance are characteristic features of Hong Kong Chinese patients who have various components of the metabolic syndrome. Obesity has a greater effect than plasma insulin on various pathophysiologies.

Adult↗
PubMed1999

Vitamin D receptor gene polymorphisms and bone mineral density in elderly Chinese men and women in Hong Kong.

Although genetic factors have been strongly implicated in determining bone mineral density (BMD), the role of the vitamin D receptor (VDR) polymorphism remains controversial. An overall consensus is difficult, as the populations studied have been heterogeneous with respect to menopausal status and ethnicity. Moreover, some studies have examined only small populations, and relatively few studies have been conducted in Asian populations. There is mounting evidence that calcium homeostasis in Asian populations differs from that in Caucasians. This difference may be mediated, in part, through VDR effects. In a cross-sectional study we have examined the relationship between the VDR polymorphism and BMD in 272 women (mean age 75 years) and 237 men (mean age 73 years) of Chinese origin from Hong Kong. Consistent with other studies in Asian populations we found higher frequencies of the T, b and a alleles compared with those reported in Caucasian populations. Moreover, no significant difference in BMD was observed when subjects were grouped by a combination of the genotypes (bbAATT, bbAaTT, bbaaTT, BbAaTt, BbAATt). These results suggest that VDR polymorphism is not associated with BMD in elderly Hong Kong Chinese men and women.

Aged↗
PubMed1999

A sibling-pair analysis of fasting lipids and anthropometric measurements and their relationship to hypertension.

Fifty non-diabetic, young Chinese hypertensives were compared to their normotensive siblings with respect to body fat distribution and fasting lipid and glucose (FPG) profiles. Sitting BP in hypertensives met conventional hypertension criteria after a 4-week washout period on placebo. Hypertensives had greater body mass index (BMI), subscapular skin-fold thickness (SFT), waist circumference (W), waist-to-height (WHtR) and waist-to-hip ratio (WHR), p<0.0001 for all. Higher triglycerides (p=0.004) and lower HDL-cholesterol (p=0.015) concentrations were also observed. Weight, W, WHtR and BMI were higher in hypertensives in both male (n=9) and female gender-concordant sibling pairs (n=21). Higher WHR, hip circumference and subscapular SFT were only seen in the male hypertensives. Hypertension is associated with central adiposity and adverse lipid profiles in this group of young hypertensives, supporting the hypothesis that obesity, particularly central, is closely associated with hypertension in Chinese as in other ethnic groups.

Adult↗
PubMed1997

Epidemic patterns and carriage of Chlamydia pneumoniae in Norway.

Chlamydia pneumoniae infection, in earlier days misdiagnosed as ornithosis, is very common in Norway. The disease develops slowly, a feature that may account for the very large number of subclinical cases, which may be seven fold more common than clinical cases. Subclinical cases produce an antibody response similar to that seen in overt clinical disease. Silent carriage of C. pneumoniae in healthy individuals may be frequent. Therapy based on positive cell culture or polymerase chain reaction (PCR) in the absence of pneumonic symptoms may be questionable. PCR has, however, given the slow development of disease, revealed itself as a handy epidemiological technique useful for the survey of healthy populations.

Carrier State↗
PubMed1997

Respiratory Chlamydial infections in a Hong Kong teaching hospital and association with coronary heart disease.

The microimmunofluorescence antibody technique was used to determine the seroprevalence of antibodies to Chlamydia pneumoniae and Chlamydia psittaci from hospitalized patients in Hong Kong. Antibodies to C. pneumoniae were found in 54.8% of 157 patients hospitalized with respiratory disease, in 71.1% of 83 patients with cardiac disease and in 31.2% of 93 patients without either respiratory or cardiac disease. Antibodies to C. psittaci were found in 0.9% of the combined study groups. There was serological evidence of C. pneumoniae being the responsible agent in 24.8% of the severe respiratory cases. A significant correlation between antibody prevalence and coronary heart disease was identified during the study.

Adult↗
PubMed1990

Selective class III antiarrhythmic agents. 1 Bis(arylalkyl)amines.

A series of bis(arylalkyl)amines is described and their effects on prolonging effective refractory period in isolated cardiac tissue listed. Most compounds prolonged the cardiac action potential without significantly altering the maximum rate of depolarization and may be defined as selective class III antiarrhythmic agents. It was found that a particularly advantageous structural feature was to have a methanesulfonamido moiety on both of the aryl rings. Thus, compound 16 [1-(4-methanesulfonamidophenoxy)2-[N-(4-methanesulfonamidophene thyl)-N- methylamine]ethane] was selected for further investigations. The compound is highly potent and selective class III agent which acts by blockade of cardiac potassium channels.

Action Potentials↗
PubMed1976

Pulmonary tuberculosis in a sulfur-crested cockatoo.

An adult, female sulfur-crested cockatoo (Kakatoe sp) was examined because of dyspnea associated with hemoptysis. On radiographic examination there was a large cystic pulmonary mass that, on aspiration, was found to contain thick sanguineous fluid. Ziehl-Neelsen staining of aspirate smears revealed numerous acid-fast organisms. Gross necropsy and microscopic findings suggested a diagnosis of tuberculosis, with primary focus of infection in the pulmonary tissues. Bacteriologic isolation and typing confirmed a diagnosis of tuberculosis and established Mycobacterium avium as the etiologic agent.

Animals↗
PubMedDate not supplied

Interethnic differences in coronary heart disease mortality in 25 populations: association with the angiotensin-converting enzyme DD genotype frequency.

BACKGROUND: Despite changes in dietary habits and steadily increasing serum cholesterol concentrations, coronary heart disease (CHD) mortality rates in developed South-East Asian populations are still one quarter those in many Western populations. We propose that genetic factors may, in part, contribute to these differences in CHD mortality. DESIGN: Using an ecological study design, we have investigated the comparative roles of serum cholesterol concentration and the angiotensin-converting enzyme (ACE) homozygote deletion (DD) genotype frequency, which has recently been implicated in CHD mortality. METHODS: Using our genotyping data from local Chinese populations, together with previously published data on ACE gene frequency and cholesterol concentrations, we correlated ACE DD genotype frequencies and mean serum cholesterol concentrations with World Health Organization age-adjusted CHD mortality rates in 25 ethnically diverse populations. RESULTS: Although mean serum cholesterol accounted for 67% of the variance in CHD mortality rates for all populations (r=0.82, 95% Cl 0.63-0.92, n=25, P<0.001), the ACE DD frequency accounted for 61% of the variance in 'low' cholesterol populations (r=0.78, 95% Cl 0.43-0.91, n= 14, P<0.001) with no additional contribution from serum cholesterol concentration. Moreover, in the 'low' cholesterol population, mean serum cholesterol accounted for only 37% of the variance. CONCLUSION: We hypothesize that differences in the frequency of the ACE DD genotype in populations with low mean serum cholesterol concentrations may play some part in determining interethnic differences in CHD mortality rates.

Adolescent↗