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Biomedical subjects

J A Critchley

Publications and source records attributed to J A Critchley.

At least 37 records · Page 2Linked to original sources
PubMed2001

Albuminuria and the renin-angiotensin system gene polymorphisms in type-2-diabetic and in normoglycemic hypertensive Chinese.

BACKGROUND: Albuminuria predicts nephropathy-related mortality in Caucasian and Chinese populations. The involvement of renin-angiotensin system (RAS) gene polymorphisms in the pathogenesis of nephropathy has been described predominantly in Caucasian populations. We have previously suggested that the angiotensinogen 235T variant may be associated with nephropathy in diabetic Chinese. PATIENTS AND METHODS: To validate these findings and extend them to include non-diabetic nephropathy, we examined the association of albuminuria and gene polymorphisms of the angiotensinogen M235T, angiotensin-converting enzyme insertion/deletion and angiotensin II type I receptor A1166C polymorphisms in 614 Chinese subjects (66% type 2 diabetic, 16% normoglycemic hypertensives and 18% controls). RESULTS: Obesity and higher blood pressure were associated with albuminuria in both diabetes and normoglycemic hypertension. In the diabetic group, albuminuria was also associated with increased insulin resistance and glycemic indices, duration of diabetes and adverse lipid profiles. Only the ACE gene polymorphism showed evidence of association with albuminuria, with the D allele being less frequent in the normoglycemic hypertensive patients with albuminuria (25.0%) than the controls (41.4%) or normoalbuminuric group (39.6%) and in those hypertensives at increased risk (albumin-to-creatinine ratio > 5.6 mg/mmol) of end-stage renal disease than those at lower risk (all p < 0.05), but not in the diabetic group. The D allele was also less prevalent in the total (31.9%) and normoalbuminuric (32.2%) diabetic groups than in the controls (p < 0.05). CONCLUSION: In this cohort of Chinese subjects, the ACE gene polymorphism D allele was less frequent in normoglycemic hypertensive patients with albuminuria and in type 2 diabetes.

Adult↗
PubMed2001

Glycaemic control and obesity are the major determinants of diabetic dyslipidaemia in Hong Kong Chinese.

OBJECTIVES: Dyslipidaemia plays a major role in the increased mortality in diabetes. Our aim was to address the quantitative abnormalities and determinants for lipid abnormalities in Chinese Type 2 diabetic patients. MATERIAL AND METHODS: In this study, we examined 1 279 Chinese type 2 diabetic patients and compared them with 959 non-diabetic control subjects. RESULTS: Of the 1 279 Type 2 diabetic patients, 588 (46.0%) were men and 691 (54.0%) were women. The mean age was 40.4 +/- 8.1 years (median: 41.0 years, range: 16-72 years). Compared to the 959 age- and sex-matched non-diabetic controls, diabetic patients were more obese, had higher blood pressure and adverse lipid profile characterized by high triglycerides and low high-density lipoprotein cholesterol. After adjusting for age, sex, smoking, obesity, use of lipid-lowering drugs and anti-diabetic agents, diabetic patients had higher risk of having hypertriglyceridaemia (>=2.3 mmol/L) and low high-density lipoprotein cholesterol (<0.9 mmol/L) than non-diabetic subjects. The corresponding odds ratios were 2.9 and 1.5, respectively. With multiple regression analysis (stepwise), dyslipidaemia was mainly associated with glycaemia, obesity and age in diabetic patients, and obesity, male gender and age in non-diabetic subjects. CONCLUSION: We have confirmed the high prevalence and increased risk of dyslipidaemia in Chinese type 2 diabetic patients. The long-term significance of these lipid abnormalities and their synergism on clinical outcomes requires further evaluation.

Adolescent↗
PubMed2001

[Studies on protective effect of total flavonoids of Astragalus on liver damage induced by paracetamol].

OBJECTIVE: To study the protective effect of total flavonoids of Astragalus (TFA) on the liver against large doses of paracetamol in mice. METHOD: After oral administration of TFA or Vitamin C 1 h prior to giving large dose of paracetamol in mice, the changes of paracetamol-induced mortality rate, serum enzyme level and liver damage degree were observed. RESULT: Paracetamol produced 80% mortality, within 24 hours of the administration of a dose of 1000 mg.kg-1 to the mice. Pre-treatment of the animals with TFA (100 mg.kg-1) or Vitamin C (1,000 mg.kg-1) reduced the death rate to 20% and 0% respectively. There was also a significant rise in the serum enzyme level of alanine transaminase (P < 0.001) and the area of liver necrosis (P < 0.001), 24 h after paracetamol (400 mg.kg-1) treatment. With pre-treatment with either TFA or Vitamin C, there was an obvious dose-dependent decrease in ALT levels and the area of hepatocellular necrosis. CONCLUSION: TFA has potential protecting effect against the paracetamol-induced hepatic damage.

Acetaminophen↗
PubMed2001

[Protection against paracetamol-induced hepatic damage using total flavonoids of Astragalus].

OBJECTIVE: To study the mechanism of the protection by total flavonoids of Astragalus protection against paracetamol-induced hepatic damage. METHOD: Analysing paracetamol and its metabolites in mice urine by HPLC and studying the mechanism of anti-damage induced by paracetamol using experiment module of pentobarbital-induced sleeping time. RESULT: Administration of large doses of paracetamol to C57BL/6J mice produced significant hepatic injury with marked elevation in serum ALT activity and severe hepatocellular necrosis. TFA showed a good protective capability against paracetamol-induced hepatic injury. TFA had no marked effect on paracetamol and its metabolites except for the mercapturate-conjugate. The concentration of mercapturate change decreased with increasing TFA dose. TFA had no effect on the pentobarbital metabolites (P > 0.05). However, paracetamol (400 mg.kg-1) prolonged the sleeping time (by 110 min relative to the controls, P < 0.001). The TFA (P < 0.005) caused significant reduction in paracetamol-prolonged pentobarbital-induced sleep. CONCLUSIONS: The mechanism of TFA's protective effect against the paracetamol-induced damage may be related to the inhibition of some metabolism progress of paracetamol and the reduction of the toxicity metabolite such as mercapturate-conjugate.

Acetaminophen↗
PubMed2000

The effect of lung injury and excessive lung fluid, on impedance cardiac output measurements, in the critically ill.

OBJECTIVES: To investigate the relationship between the attenuation of impedance cardiac output (IC(co)) measurements and lung fluid content in critically ill patients. DESIGN: Observational study. SETTING: Intensive Care Unit of a major teaching hospital in Hong Kong. PATIENTS: Twenty-four critically ill patients who required a pulmonary artery catheter. MEASUREMENTS AND MAIN RESULTS: Triplicate thermodilution cardiac output (TD(co)) and BoMed NCCOM3 (IC(co)) measurements were made simultaneously on a single occasion in each patient. Lung fluid accumulation was assessed by: (a) thoracic impedance (Zo), (b) radiological assessment of chest X-rays using an alveolar consolidation score (0-4) and (c) scoring the degree of hypoxia and use of positive end-expiratory pressure (PEEP). Offsets (TD(co)-IC(co))/TD(co), expressed as percentage, were compared with these indices of excess lung fluid. Patients were divided into those with sepsis (n = 13), fluid balance problems (n = 5) and cardiothoracic problems (n = 6). Mean cardiac output values were: 6.7 l/min TD(co) (range 3.6-12.9) and 5.2 l/min IC(co) (range 2.7-9.0). Overall the TD(co) and IC(co) values showed great variance, with a bias and limits of agreement of 1.49 +/- 4.16 l/min, or +/- 69%. In septic patients, increasing offset was correlated with decreases in Zo (r = 0.73, P = 0.005) and increases in alveolar consolidation score (r = 0.72, P = 0.005). CONCLUSIONS: The BoMed under-estimates cardiac output in critically ill patients. In septic patients the degree of attenuation of IC(co) can be related to the extent of lung injury and fluid accumulation within the thorax.

Adult↗
PubMed2000

Effects and pharmacokinetics of oral glibenclamide and glipizide in Caucasian and Chinese patients with type-2 diabetes.

The effects and kinetics of oral glibenclamide (Gb) and glipizide (Gz) were studied in Caucasian and Chinese patients (ten in each group) with type-2 diabetes. In randomised order, 2.5 mg Gb, 2.5 mg Gz or placebo was given orally before the administration of 75 g oral glucose. Concentrations of insulin and proinsulin were determined using radioimmunoassay (RIA) without cross-reactivities, and sulphonylurea concentrations were determined using high-performance liquid chromatography (HPLC). There were no significant interethnic differences in Gb or Gz effects whether on glucose, insulin or proinsulin/insulin ratio at any time point. Following Gz, however, Chinese patients had greater increments of serum proinsulin at 10-30 min compared with Caucasians. Apart from the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of Gz being higher among the Chinese, no significant interethnic differences in pharmacokinetics were found. It appears that the same dosage principles could be used for Caucasian and Chinese patients with type-2 diabetes when Gb or Gz are prescribed.

Adult↗
PubMed2000

Pharmacodynamics and pharmacokinetics of intravenous glibenclamide in Caucasian and Chinese patients with type-2 diabetes.

OBJECTIVE: We analysed the kinetics and effects of glibenclamide (Gb) on glucose, insulin and proinsulin secretion in two ethnic groups (10 in each) of type-2 diabetic patients, one of Caucasian, the other of Chinese origin. BACKGROUND: Diabetes mellitus type 2 is a global disease affecting all ethnic groups. There are ethnic differences in both the prevalence and metabolic characteristics of the disease. Important interethnic pharmacodynamic and pharmacokinetic differences have been reported for several drugs. With few exceptions, detailed studies on sulphonylurea are lacking. MATERIAL AND METHODS: The patients were studied on two occasions when either no Gb (control) or 1.25 mg Gb was administered i.v., immediately before the administration of a 75-g oral glucose tolerance test. Concentrations of insulin and proinsulin were determined by means of radioimmunoassay without cross-reactivities. Gb concentration was determined using high-performance liquid chromatography. Pharmacodynamic results were calculated using net areas under the curves, with basal values set as zero. A P value less than 0.05 was considered significant. RESULTS: When glucose was administered orally without Gb, Chinese patients had higher plasma glucose increases at 10 min (7.6 mmol/l x min vs 2.6 mmol/l x min) and higher increases of plasma insulin levels than Caucasians at both 10 min (198 pmol/l x min vs 54 pmol/l x min) and 30 min (2286 pmol/l x min vs 1198 pmol/l x min). When Gb was administered, the plasma glucose increases were reduced, and the increases of serum insulin and proinsulin levels were greater in both ethnic groups. Compared with the basal values (-1 min), proinsulin/insulin ratios (RPI) were lowest at 10-30 min, followed by an increase. Chinese patients had higher increases of serum insulin levels at 10 min (1109 pmol/l x min vs 550 pmol/l x min) and a lower RPI at 30 min (6. 0% vs 7.6%) and 240 min (15.0% vs 21.0%) relative to Caucasians. Serum Gb data were best fitted to a biexponential i.v. model. There were no interethnic differences in any of the pharmacokinetic parameters. CONCLUSION: In summary, following oral glucose administration without Gb, Chinese type-2 diabetic patients had higher plasma insulin levels but also higher plasma glucose levels during the first 10 min, which might reflect reduced insulin sensitivity or more rapid glucose absorption. Gb augmented glucose-induced release of both insulin and proinsulin in both ethnic groups; the effect on insulin secretion was more pronounced. In conclusion, minor pharmacodynamic but no pharmacokinetic differences were found between the two groups. It seems appropriate to employ the same dosage principles when using Gb in Caucasians and Chinese.

Adult↗
PubMed2000

Cardiovascular disease in chinese type 2 diabetic women is associated with a prolonged QTc interval.

We studied the relationships between QT interval and cardiovascular disease status in 192 Chinese type 2 diabetic patients. Of these 192 subjects, 132 (68.8%) were women and 60 (31.2%) were men. The mean age (+/-S.D.) was 56.6+/-12.9 years (range: 23-84, median: 58.0 years). Women had longer QTc interval compared to men (0.402+/-0.030 s vs. 0.387+/-0.026 s, P<0.01). Of the 192 subjects, 18 women and two men had prolonged QTc interval (QTc >0.433 s). Women with prolonged QTc interval have a 2.8-fold greater rate of cardiovascular disease as compared to those with normal QTc interval (38.9% vs. 14.0%, P<0.05). Using multiple regression analysis (stepwise) to assess the relationship with QTc interval with age, sex, body mass index, waist-hip ratio, blood pressure, fasting plasma glucose, glycated haemoglobin, lipid profiles, smoking and duration of diabetes as independent variables (R(2)=0.146, F=8.88, P<0.001), systolic blood pressure (beta=0.198, P=0.017), age (beta=0. 189, P=0.023) and female gender (beta=0.157, P=0.037) were found to be independently associated with QTc interval. In conclusion, we have shown a significant association between prolonged QTc interval, ischaemic heart disease and cardiovascular disease in Chinese type 2 diabetic women. Age, systolic blood pressure and female gender are independently correlated to QTc interval.

Adult↗
PubMed2000

An insulin receptor gene polymorphism is associated with diastolic blood pressure in Chinese subjects with components of the metabolic syndrome.

Insulin resistance has been described as a possible underlying link for the clustering of Type 2 diabetes mellitus, hypertension, obesity, and dyslipidemia, known as the metabolic syndrome. Mutations within the insulin receptor have been associated with hypertension in some white and Oriental populations. We examined the relationship between the insulin receptor NsiI restriction fragment-length polymorphism (RFLP) and biochemical and anthropometric parameters associated with these disorders in 933 Chinese subjects. Of the 933 subjects, 117 were control subjects and 816 had one or more components of the metabolic syndrome: 59.7% hypertension, 64.6% glucose intolerance, 55.3% dyslipidemia, and 53.3% obesity. The prevalences of the N1 allele and N1N1 genotype were 74.4% and 55.8%, respectively, in the whole population. No differences were observed in the genotype and allele frequency distributions between the control group and the cohorts with glucose intolerance, hypertension, or dyslipidemia alone or in combination. Using one-way ANOVA, there was a weak relationship between the insulin receptor genotypes and diastolic blood pressure (DBP), P = .069. The DBP was significantly higher in subjects carrying the N1N1 genotype in both the total population (80 +/- 13 v 76 +/- 12 mm Hg, P = .038) and subjects with glucose intolerance (80 +/- 12 v 76 +/- 10 mm Hg, P = .048). Using stepwise multiple regression, the insulin receptor NsiI polymorphism was found to be an independent predictor of DBP in this Chinese population, P = .018. Age, gender, and body mass index (BMI) were also included in the analysis and were all significantly associated with diastolic DBP. To conclude, the insulin receptor gene NsiI RFLP is associated with DBP in these Chinese subjects.

Adult↗
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

Mitochondrial DNA A3243G mutation in patients with early- or late-onset type 2 diabetes mellitus in Hong Kong Chinese.

BACKGROUND AND OBJECTIVES: The mitochondrial DNA A to G mutation at nucleotide 3243 (mt3243) is associated with a subtype of diabetes characterized by maternal transmission and deafness. We have previously reported a 2.7% prevalence of this mutation in a cohort of young patients with either type 1 or type 2 diabetes. In this study, we aimed to confirm this finding by examining for the prevalence of this mutation in a large-scale study. SUBJECTS AND METHODS: Nine hundred and six unrelated Chinese patients with type 2 diabetes and 213 nondiabetic controls were studied. The presence of mt3243 mutation was determined by polymerase chain reaction amplification and ApaI digestion. RESULTS: This mutation was found in four of 133 (3.0%) patients with early onset (</= 40 years) diabetes who also had a positive maternal family history, and in one of 348 (0.3%) patients with late-onset (> 40 years) diabetes and no family history. Basal pancreatic beta-cell function, as assessed by fasting plasma C-peptide, was variable amongst mutation carriers, and did not correlate with the level of heteroplasmy of mutation. CONCLUSIONS: In agreement with most studies, our results suggest that despite the high prevalence of positive maternal family history of diabetes amongst our type 2 diabetic patients, mt3243 mutation was not a major cause of diabetes in either early- or late-onset diabetic patients in Hong Kong. The role of other genetic, environmental and intrauterine factors needs further investigation.

Adult↗
PubMed2000

Renal kallikrein-kinin system, but not renal dopamine system, mediates the natriuretic response to intravenous saline infusion in healthy Chinese subjects.

1. To assess the role of renal dopamine (DA), sympathetic nervous system (SNS) activity and the renal kallikrein-kinin system in sodium excretion in Chinese subjects, we studied the effects of intravenous saline infusion on the urinary excretions of sodium, free DA, free noradrenaline (NA) and kallikrein in eight healthy males aged 23-25 years. 2. After a baseline period of 1 h (hour 0), these subjects received 11 of 0.9% saline over 2 h (hours 1 and 2), followed by a 4-h recovery period (hours 3-6). From hours 0-4, subjects remained in the supine position, except to void urine. Distilled water was given orally throughout the study to ensure an adequate diuresis. 3. A 31-39% increase in sodium excretion (P < 0.05) was seen during hours 2 and 3. Urinary DA did not change throughout the study period. Urinary free NA showed no changes while the subjects remained supine, but an increase of 91-105% (P < 0.02) was seen after the subjects became ambulatory. However, there was a 103-140% increase in urinary kallikrein excretion (P < 0.05) during the saline infusion. Urinary kallikrein was still much higher (by 74%) than the basal level 1 h after the completion of the saline infusion. 4. There is no evidence from the present study that renal DA or SNS play any role in the natriuretic response to saline infusion in Chinese subjects. The brisk urinary kallikrein response, despite a relatively small salt load, suggests that the renal kallikrein-kinin system may play an important role in extracellular fluid volume and sodium homeostasis in Chinese subjects.

Adult↗
PubMed2000

Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients.

UNLABELLED: Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients. BACKGROUND: In hypertensive type 2 diabetic patients, treatment with angiotensin-converting enzyme (ACE) inhibitors is associated with a lower incidence of cardiovascular events than those treated with calcium channel-blocking agents. However, the long-term renal effects of ACE inhibitors in these patients remain inconclusive. In 1989, we commenced a placebo-controlled, double-blind, randomized study to examine the anti-albuminuric effects of enalapril versus nifedipine (slow release) in 102 hypertensive, type 2 diabetic patients. These patients have been followed up for a mean trial duration of 5.5 +/- 2.2 years. We examined the determinants, including the effect of ACE inhibition on clinical outcomes in these patients. METHODS: After a six-week placebo-controlled, run-in period, 52 patients were randomized double-blind to receive nifedipine (slow release) and 50 patients to receive enalapril. After the one-year analysis, which confirmed the superior anti-albuminuric effects of enalapril (-54%) over nifedipine (+11%), all patients were continued on their previously assigned treatment with informed consent. They were subdivided into normoalbuminuric (N = 43), microalbuminuric (N = 34), and macroalbuminuric (N = 25) groups based on two of three 24-hour urinary albumin excretion (UAE) measurements during the run-in period. Renal function was shown by the 24-hour UAE, creatinine clearance (CCr), and the regression coefficient of the yearly plasma creatinine reciprocal (beta-1/Cr). Clinical endpoints were defined as death, cardiovascular events, and/or renal events (need for renal replacement therapy or doubling of baseline plasma creatinine). RESULTS: In the whole group, patients treated with enalapril were more likely to revert to being normoalbuminuric (23.8 vs. 15.4%), and fewer of them developed macroalbuminuria (19.1 vs. 30.8%) compared with the nifedipine-treated patients (P < 0.05). In the microalbuminuric group, treatment with enalapril (N = 21) was associated with a 13.0% (P < 0.01) reduction in 24-hour UAE compared with a 17.3% increase in the nifedipine group (N = 13). In the macroalbuminuric patients, enalapril treatment (N = 11) was associated with stabilization compared with a decline in renal function in the nifedipine group, as shown by the beta-1/Cr (0.65 +/- 4.29 vs. -1.93 +/- 2.35 1/micromol x 10-3, P < 0.05) after adjustment for baseline values. Compared with the normoalbuminuric and microalbuminuric patients, those with macroalbuminuria had the lowest mean CCr (75.5 +/- 24.1 vs. 63.5 +/- 21.3 vs. 41.9 +/- 18.5 mL/min, P < 0.001) and the highest frequency of clinical events (4.7 vs. 5.9 vs. 52%, P < 0. 001). On multivariate analysis, beta-1/Cr (R2 = 0.195, P < 0.001) was independently associated with baseline HbA1c (beta = -0.285, P = 0.004), whereas clinical outcomes (R2 = 0.176, P < 0.001) were independently related to the mean low-density lipoprotein cholesterol (beta = 2.426, P = 0.018), high-density lipoprotein cholesterol (beta = -8.797, P = 0.03), baseline UAE (beta = 0.002, P = 0.04), and mean CCr during treatment (beta = -0.211, P = 0.006). CONCLUSION: In this prospective cohort analysis involving 102 hypertensive, type 2 diabetic patients with varying degrees of albuminuria followed up for a mean duration of five years, we observed the importance of good metabolic and blood pressure control on the progression of albuminuria and renal function. Treatment with enalapril was associated with a greater reduction in albuminuria than with nifedipine in the entire patient group, and especially in those with microalbuminuria. In the macroalbuminuric patients, the rate of deterioration in renal function was also attenuated by treatment with enalapril.

Aged↗
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↗