Biomedical subjects

Wing-Yee So

Publications and source records attributed to Wing-Yee So.

At least 19 recordsLinked to original sources

PubMed2007

Bayesian analysis of structural equation models with multinomial variables and an application to type 2 diabetic nephropathy.

There is now increasing evidence proving that many complex diseases can be significantly influenced by correlated phenotype and genotype variables, as well as their interactions. Effective and rigorous assessment of such influence is difficult, because the number of phenotype and genotype variables of interest may not be small, and a genotype variable is an unordered categorical variable that follows a multinomial distribution. To address the problem, we establish a novel nonlinear structural equation model for analysing mixed continuous and multinomial data that can be missing at random. A confirmatory factor analysis model with Kronecker product is proposed for grouping the manifest continuous and multinomial variables into latent variables according to their functions; and a nonlinear structural equation is formulated to assess the linear and interaction effects of the independent latent variables to the dependent latent variables. Bayesian methods for estimation and model comparison are developed through Markov chain Monte Carlo techniques and path sampling. The newly developed methodologies are applied to a case-control cohort of type 2 diabetic patients with nephropathy.

Bayes Theorem↗

PubMed2007

Development and validation of stroke risk equation for Hong Kong Chinese patients with type 2 diabetes: the Hong Kong Diabetes Registry.

OBJECTIVE: We sought to develop stroke risk equations for Chinese patients with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS: A total of 7,209 Hong Kong Chinese type 2 diabetic patients without a history of stroke at baseline were analyzed. The data were randomly and evenly divided into the training subsample and the test subsample. In the training subsample, stepwise Cox models were used to develop the risk equation. Validation of the U.K. Prospective Diabetes Study (UKPDS) stroke risk engine and the current stroke equation was performed in the test dataset. The life-table method was used to check calibration, and the area under the receiver operating characteristic curve (aROC) was used to check discrimination. RESULTS: A total of 372 patients developed incident stroke during a median of 5.37 years (interquartile range 2.88-7.78) of follow-up. Age, A1C, spot urine albumin-to-creatinine ratio (ACR), and history of coronary heart disease (CHD) were independent predictors. The performance of the UKPDS stroke engine was suboptimal in our cohort. The newly developed risk equation defined by these four predictors had adequate performance in the test subsample. The predicted stroke-free probability by the current equation was within the 95% CI of the observed probability. The aROC was 0.77 for predicting stroke within 5 years. The risk score was computed as follows: 0.0634 x age (years) + 0.0897 x A1C + 0.5314 x log(10) (ACR) (mg/mmol) + 0.5636 x history of CHD (1 if yes). The 5-year stroke probability can be calculated by: 1 - 0.9707(EXP (Risk Score - 4.5674)). CONCLUSIONS: Although the risk equation performed reasonably well in Chinese type 2 diabetic patients, external validation is required in other populations.

Asian People↗

PubMed2006

Overweight, family history of diabetes and attending schools of lower academic grading are independent predictors for metabolic syndrome in Hong Kong Chinese adolescents.

BACKGROUND: Overweight and metabolic syndrome (MES) are emerging in both adult and paediatric populations. AIMS: To study the prevalence of and associated risk factors for the MES, using the National Cholesterol Education Program definition, among Hong Kong Chinese adolescents studying in secondary schools. METHODS: This was a cross-sectional, population-based study. A sample of 2115 Chinese adolescents was randomly selected from 14 secondary schools throughout Hong Kong. Data on anthropometric parameters, fasting blood and urine samples were collected in the school setting. Information regarding the adolescent's family history of diabetes, perinatal history, socioeconomic status and school grading was evaluated. RESULTS: The prevalence of MES was 2.4% (95% confidence interval (CI) 1.8 to 3.1), with no significant difference between boys (2.9%) and girls (2%). The prevalence of various components of MES was 32.2% (30.2 to 34.2) for hypertension, 10.9% (9.6 to 12.2) for increased triglyceride, 9.0% (7.8 to 10.2) for central adiposity, 2.4% (1.7 to 3) for low high-density lipoprotein cholesterol and 0.3% (0.1 to 0.6) for impaired fasting glucose. On multivariate analysis, overweight (odds ratio 32.2; 95% CI 13.2 to 78.4), positive family history of diabetes (4.3; 1.3 to 14.1) and studying at schools of lower academic grading (5.5; 2.2 to 13.7) were found to be independent risk factors for MES. CONCLUSION: A comparable prevalence of MES (2%) is observed in our study group Chinese adolescent girls and in US girls (2.1%), but a lower prevalence in Chinese boys (2.9%) than in US boys (6.1%). In our study, 41.8% harbour at least one component of the syndrome. Both families and schools should be alerted to this growing epidemic.

Adolescent↗

PubMed2006

Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are reaching epidemic levels worldwide, but data in Asia remain scarce. This cross-sectional study examined the metabolic and adipokine profiles of Chinese patients with biopsy-proven NAFLD and factors associated with severe disease. METHODS: Eighty ethnic Chinese with NAFLD and 41 healthy controls were recruited. Metabolic parameters and fasting adiponectin, tumor necrosis factor-alpha (TNF-alpha), leptin, and resistin levels were measured on the day of liver biopsy. Histology was scored according to Brunt's criteria. Metabolic syndrome was assessed by using both the International Diabetes Federation and Adult Treatment Panel III criteria. RESULTS: Twenty-eight patients had simple steatosis, and 52 patients had nonalcoholic steatohepatitis (NASH), defined as necroinflammatory grade >/=2 and/or fibrosis by Brunt's criteria. The ethnic-specific International Diabetes Federation criteria identified more cases of metabolic syndrome among NAFLD patients than the Adult Treatment Panel III criteria (70% vs 56%, P < .0001). On multivariate analysis, low adiponectin level, increased leptin level, and diabetes mellitus were associated with NAFLD. High TNF-alpha level and high body mass index were independent factors associated with NASH. TNF-alpha level had positive correlation with necroinflammatory grade (R = .35, P = .002) and fibrosis stage (R = .31, P = .005). CONCLUSIONS: Hypoadiponectinemia and elevated TNF-alpha levels are associated with the development of NAFLD and NASH, respectively, independent of other metabolic factors. Ethnic-specific definition of metabolic syndrome is more useful in the assessment of NAFLD patients.

Adiponectin↗

PubMed2006

Intragastric balloon in ethnic obese Chinese: initial experience.

BACKGROUND: We evaluated the effectiveness and safety of intragastric balloon (IGB) for the treatment of obesity in ethnic Chinese in Hong Kong. METHODS: 15 Chinese patients (10 females; median age 40 years (range 21-58)) completed IGB treatment over a 10-month period since November 2004. Median baseline body weight (BW) and BMI were 100.1 (range 78.5-170.3) kg and 39.4 (range 29.6-56.9) kg/m2 respectively. Coexistent obesity-related morbidities were present in 80% of patients. The Bioenterics Intragastric Balloon (BIB) was employed, and all placement and removal were performed endoscopically under intravenous conscious sedation. A restricted balanced diet (approximately 1200 kcal/day) and 150 minutes/week of moderate-intensity exercise were prescribed after balloon placement in a multidisciplinary approach. Outcome measures were collected and assessed in a prospective manner. RESULTS: Median procedure time was 25 (range 19-45) minutes and median hospital stay was 2 (range 1-6) days. Median BW and BMI loss were 15.3 (range 5.3-30.9) kg and 5.6 (range 1.9-12.5) kg/m2 after IGB. The median waist circumference (WC) loss was 9 (range 4-23) cm, and 66.7% of patients were highly satisfied with the treatment. No serious complication related to IGB was observed. CONCLUSION: IGB is a safe and effective device that achieves moderate weight loss in obese ethnic Chinese patients.

Adult↗

PubMed2006

Hematocrit, independent of chronic kidney disease, predicts adverse cardiovascular outcomes in chinese patients with type 2 diabetes.

OBJECTIVE: Anemia and chronic kidney disease (CKD) are risk factors for cardiovascular diseases in diabetes. We examined the association between hematocrit, stratified by the presence of CKD, and cardiovascular events in a cohort of Chinese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 3,983 patients who underwent assessment for diabetes complications were recruited. Subjects were categorized into five groups. Group I included subjects with hematocrit below the normal sex-specific range. The cutoff points for groups II-V were selected to represent the distribution of the hematocrit for each sex. CKD was defined by the estimated glomerular filtration rate <60 ml/min per 1.73 m(2). Cardiovascular events were defined as cardiovascular mortality and morbidity, including new onset of myocardial infarction, acute coronary syndrome, revascularization, heart failure, and stroke requiring hospitalization. RESULTS: A total of 294 subjects (7.4%) developed cardiovascular events during the median of 36.4 months. The rate of cardiovascular events was highest in subjects with low hematocrit (group I, 18.6%) compared with group V (3.4%, P < 0.001). The multivariate-adjusted hazard ratio for cardiovascular events diminished with increasing hematocrit (group I, 1.0; group II, 0.73 [95% CI 0.51-1.04]; group III, 0.57 [0.39-0.83]; group IV, 0.61 [0.39-0.95]; and group V, 0.36 [0.17-0.79]). After stratifying by the presence of CKD, the previously observed reduction in the risk of developing cardiovascular events with increasing hematocrit was abolished in the cohort with CKD but persisted in the non-CKD cohort. CONCLUSIONS: In Chinese subjects with type 2 diabetes, low levels of hematocrit and the presence of CKD are associated with increased risk of developing adverse cardiovascular events.

Adult↗

PubMed2005

Association of testosterone, insulin-like growth factor-I, and C-reactive protein with metabolic syndrome in Chinese middle-aged men with a family history of type 2 diabetes.

CONTEXT: Age-related declines in testosterone and IGF-I are associated with deposition of visceral fat, a component of the metabolic syndrome (MES). OBJECTIVE: Testosterone and IGF-I may interact with familial disposition to diabetes mellitus to increase the association with MES. DESIGN: We conducted a cross-sectional cohort study. SETTING: The study was conducted in a university teaching hospital. SUBJECTS: Study subjects included 179 middle-aged men with a family history of diabetes (FH) (aged 39.1 +/- 8.1 yr) and 128 men without FH (aged 43.8 +/- 8.5 yr). MAIN OUTCOME MEASURES: Clinical characteristics, frequency of MES using the World Health Organization criteria with Asian definitions of obesity (body mass index > or = 25 kg/m2), and serum levels of total testosterone, IGF-I, and high-sensitive C-reactive protein (hs-CRP) were measured. RESULTS: Men with FH had higher frequency of MES than those without FH [39.1 vs. 23.4% (P = 0.004)]. On multivariate analysis, smoking (former and current smokers), low total testosterone, and IGF-I but elevated hs-CRP levels explained 35% of the MES variance in men with FH. The frequency of MES increased with declining tertiles of total testosterone and IGF-I but increasing tertiles of hs-CRP. After adjustment for age and smoking history, subjects with all three risk factors had a 13-fold increase in risk association with MES compared with those without hormonal and inflammatory risk factors. These risk associations were not found in men without FH in whom only smoking (ex and current) and low total testosterone level were independent predictors for MES, which explained 14% of the variance. CONCLUSIONS: Clustering of FH, hormonal abnormalities, and high hs-CRP is associated with MES in Chinese middle-aged men.

Adult↗

PubMed2005

Association between tumour necrosis factor-alpha G-308A polymorphism and risk of nephropathy in obese Chinese type 2 diabetic patients.

BACKGROUND: The G-308A polymorphism in the promoter region of the tumor necrosis factor alpha (TNF-alpha) gene has been reported to be associated with insulin resistance and obesity, both of which may increase the risk of diabetic nephropathy. We hypothesized that this polymorphism might interact with obesity to affect development of diabetic nephropathy. METHODS: A consecutive cohort of 1281 Chinese type 2 diabetic patients was enrolled for analysis. Genotyping of TNF-alpha G-308A polymorphism was performed using a PCR-based RFLP method with NcoI digestion. The mean value of the albumin creatinine ratio (ACR) of a random spot urine sample and a timed urinary collection was used to determine albuminuric status. Diabetic nephropathy was defined as serum creatinine > or =150 micromol/L and/or mean ACR > or =25 mg/mmol. Obesity was defined as body mass index > or =25 kg/m2 using Asian criteria. RESULTS: The G-308A polymorphism was not associated with either obesity or nephropathy. Clinical characteristics were similar between GG and GA/AA genotype carriers. Amongst the obese patients, GG genotype carriers had a higher median (interquartile range) urinary ACR [3.16 (0.70, 59.10) vs 1.28 (0.48, 12.28) mg/mmol; p = 0.01] and albumin excretion rate [38.7 (12.1, 620.3) vs 21.4 (8.9, 224.0) microg/min, p = 0.03] than GA/AA carriers. On multiple logistic regression analysis, compared with non-obese GA/AA carriers, obese subjects with the GG genotype had a 2.5-fold increased risk (95% CI: 1.04-6.03; P = 0.04) of nephropathy after adjustment for confounding factors. Other independent factors for diabetic nephropathy included male sex, systolic blood pressure, triglycerides (logarithmically transformed value), and the presence of cardiovascular and microvascular complications. CONCLUSION: Our findings suggest that the GG genotype of TNF-alpha G-308A polymorphism or a genetic variant in close linkage disequilibrium may interact with obesity to increase the risk of nephropathy in Chinese Type 2 diabetic patients. Apart from the need for replication of these results, functional studies are required to clarify its significance.

Aged↗

PubMed2005

Effects of body mass index, plasma glucose and cholesterol levels on isolated systolic hypertension.

Despite the high cardiovascular risk of diabetic patients, there is a paucity of data on isolated systolic hypertension (ISH) in diabetic patients. In this cross-sectional study, we examined the risk of ISH and its associated factors in Chinese type 2 diabetic patients. Isolated systolic hypertension was defined as systolic blood pressure (SBP) > or =140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg. The mean value of two BP measurements taken 1 min apart was used. There were 1048 type 2 diabetic patients recruited from the Prince of Wales Hospital Diabetes Clinic. Another 1043 age- and sex-matched non-diabetic subjects were recruited from the community. The mean age of the 2091 subjects was 40.6 +/- 7.6 years (median: 40 years, range: 16-69 years). Diabetic patients had an increased risk of ISH compared to non-diabetic subjects (7.6% vs. 3.4%, p < 0.001) with an odd ratio of 2.38. On multivariate analysis, age, body mass index, total cholesterol and duration of diabetes in diabetic subjects while age and waist-hip ratio (WHR) in non-diabetic subjects were independently associated with ISH. In conclusion, Chinese type 2 diabetic patients had increased risk to develop ISH than non-diabetic subjects. Age, obesity, lipid and duration of diabetes were independent associated with ISH. These findings suggest that control of body weight and metabolic profile might have beneficial effects on ISH.

Adolescent↗

PubMed2005

High prevalence of metabolic syndrome in Hong Kong Chinese--comparison of three diagnostic criteria.

The World Health Organisation (WHO), European Group for the Study of Insulin Resistance (EGIR) and National Cholesterol Education Program (NCEP) Expert Panels had introduced definitions for the metabolic syndrome (MES). We aimed to estimate the prevalence of MES in a working population in Hong Kong using the three definitions for MES and compare their relative significance. The data are obtained from a prevalence survey for glucose intolerance and lipid abnormality in a Hong Kong Chinese working population. The distribution of occupational groups in these subjects was similar to that recorded in the Hong Kong Census (1991) and representative of the Hong Kong working population. Definition of obesity was modified using the Asian criterion of body mass index (BMI)> or =25 kg/m 2, waist circumference>80 cm in women and >90 cm in men. Of the 1513 subjects, 910 (60.1%) were men and 603 (39.9%) were women. The mean age was 37.5+/-9.2 (median 37.0 years, range 18-66 years). Using the Asian definition for obesity, the prevalence of MES using the WHO criterion was the highest (WHO versus EGIR versus NCEP-overall: 13.4% versus 8.9% versus 9.6%, p<0.001; under age of 40 years: 7.9% versus 4.9% versus 5.4%, p=0.017; age of 40 years or above: 21.9% versus 14.9% versus 16.0%, p=0.003). The prevalence of different components of the MES ranged from 6 to 38%. In subjects aged less than 50 years, there was a male preponderance for MES (male versus female-WHO: 9.5% versus 6.2%, p=0.007; EGIR: 7.9% versus 6.2%, p=0.235; NCEP: 9.5% versus 6.2%, p=0.030) but this trend was reversed after the age of 50 years (WHO: 29.3% versus 31.9%, p=0.721; EGIR: 13.1% versus 34.8%, p=0.001; NCEP: 19.2% versus 23.2%, p=0.533). The prevalence of MES in Hong Kong Chinese of working age ranges from 6.1 to 13.4% depending on various diagnostic criteria. There was a male preponderance before the age of 50 years and a female-preponderance after the age of 50 years. The inclusion of albuminuria and insulin resistance by the WHO has made it the most discriminative criterion in identifying at risk individuals in all age groups.

Adult↗

PubMed2005

Effects of structured care by a pharmacist-diabetes specialist team in patients with type 2 diabetic nephropathy.

PURPOSE: We developed a disease management program for patients with Type 2 diabetic nephropathy and evaluated its effects on the time to onset of end-stage renal disease or all-cause death compared with usual care. METHODS: In a 2-year, prospective cohort study, we compared the clinical outcomes of patients managed by a structured care protocol (n = 80) to a group receiving usual care (n=80) in the same hospital. Patients aged < or =80 years with type 2 diabetes, serum creatinine 150-400 micromol/L, and micro- or macroalbuminuria were recruited. The structured care protocol was implemented by a pharmacist-diabetes specialist team with particular emphasis on periodic laboratory assessments, patient adherence, risk factors control, and use of renin-angiotensin system inhibitor. The primary endpoint was the composite of end-stage renal disease or all-cause death. Other endpoints were the rate of renal decline, processes-of-care measures, and control of risk factors. RESULTS: During 22.8+/-7.9 months of follow-up, the primary endpoint developed in 24 and 40 patients in the structured care and usual care groups, respectively (adjusted risk reduction, 60%, P< .001). Structured care (hazard ratio [95% confidence interval (CI)], 0.40 [0.23-0.68]), age (0.95 [0.93-0.98]), baseline systolic blood pressure (BP) (1.014 [1.003-1.026]), logarithm (base 10) of baseline serum creatinine (34 441 [2290-517915]), and macroalbuminuria (8.95 [1.22-65.38]) were independent predictors for the primary endpoint. Structured care slowed the rate of renal decline (P=.032). More intensive laboratory measurements, increased use of renin-angiotensin system inhibitor, and greater reductions in BP and low-density lipoprotein (LDL) cholesterol were reported by patients receiving structured care. CONCLUSIONS: Structured care delivered by a pharmacist-diabetes specialist team reduced the incidence of end-stage renal disease or death compared with usual care in patients with type 2 diabetic nephropathy.

Adult↗

PubMed2005

Effect of hepatic lipase -514C->T polymorphism and its interactions with apolipoprotein C3 -482C->T and apolipoprotein E exon 4 polymorphisms on the risk of nephropathy in chinese type 2 diabetic patients.

OBJECTIVE: Triglyceride-rich lipoprotein particles may promote the progression of diabetic nephropathy. Patients with diabetic nephropathy have increased plasma triglycerides and reduced activity of hepatic lipase (HL), which hydrolyzes triglycerides. We hypothesized that the HL -514C-->T polymorphism, which reduces HL expression, and its interactions with polymorphisms in apolipoprotein (apo) E and apoC3 increase the risk of diabetic nephropathy. RESEARCH DESIGN AND METHODS: In a case-control study involving 374 Chinese type 2 diabetic patients with and 392 without diabetic nephropathy, we genotyped the HL -514C-->T, apoE exon 4, and apoC3 -482C-->T polymorphisms. RESULTS: HL -514T-containing genotypes (T+) were associated with diabetic nephropathy (OR = 1.7, P = 0.0009). Adjustment by multiple logistic regression for hypertension, triglycerides, sex, non-HDL cholesterol, BMI, smoking, and alcohol intake did not diminish the association (OR = 1.8, P = 0.003). The association between HL T+ genotypes and diabetic nephropathy appeared stronger in diabetic patients with apoC3 -482 non-TT genotypes (OR = 1.9, P = 0.003) or apoE epsilon2 or epsilon4 alleles (OR = 2.2, P = 0.005). Subjects with HL TT exhibited trends toward increased triglyceride and non-HDL cholesterol levels compared with CC carriers. CONCLUSIONS: HL T+ genotypes might increase the risk of developing diabetic nephropathy by slowing clearance of triglyceride-rich remnant lipoproteins. In concert with other risk factors (e.g., hyperglycemia), lipid abnormalities may damage the kidneys and endothelium, where reduced binding sites for lipases may precipitate a vicious cycle of dyslipidemia, proteinuria, and nephropathy.

Apolipoprotein C-III↗

PubMed2004

The renoprotective effects of structured care in a clinical trial setting in type 2 diabetic patients with nephropathy.

BACKGROUND: The RENAAL Study has confirmed the renoprotective effects of Losartan in type 2 diabetes. In this subgroup analysis from the RENAAL Study, we hypothesized that the intensive care received by patients in a clinical trial setting also reduced the rate of decline in renal function through optimization of all risk factors. METHODS: We compared the rate of deterioration in renal function, expressed as the regression coefficient of the monthly serum creatinine (SeCr) reciprocal (beta-1/Cr) in 55 Chinese type 2 diabetic patients before and after entry into the RENAAL Study. RESULTS: Of the 55 patients, 44 had at least three out-patient SeCr measurements both before (2.9+/-2.4 years) and after (3.3+/-0.8 years) entry into the study for evaluation. In the Losartan group (n = 24), the median beta-1/Cr fell from -11.4 x 10(-5) l micro mol(-1) month(-1) before entry into the trial to -4.7 x 10(-5) l micro mol(-1) month(-1) following entry (P = 0.001). The respective figures were -9.1 x 10(-5) and -5.0 x 10(-5) l micro mol(-1) month(-1) (P = 0.01) in the placebo group (n = 20). A decrease in beta-1/Cr was observed in 21 (87.5%) and 14 (70.0%) patients in the Losartan and placebo groups, respectively. Spot urinary albumin-to-creatinine ratio was reduced by 56% (P = 0.001) in the Losartan group but the change was not significant in the placebo group. At the end of the study, patients in both groups had lower blood pressure and better lipid control. The frequency of patient visits to doctors and nurses were doubled. CONCLUSIONS: The rate of renal function decline was significantly reduced in the majority of patients allocated to either Losartan or placebo following entry into the RENAAL study. These results suggest that in patients with diabetic nephropathy, implementation of a structured care protocol in a clinical trial setting facilities intensive treatment of risk factors confering renoprotective effects in addition to those resulting from Losartan treatment.

Aged↗

PubMed2004

The metabolic effects of insulin and rosiglitazone combination therapy in Chinese type 2 diabetic patients with nephropathy.

BACKGROUND: Few studies have examined the efficacy and safety of thiazolidinedione use in patients with diabetic nephropathy. Our goal was to examine the metabolic effects and tolerability of combination therapy with rosiglitazone and insulin in type 2 diabetic patients with nephropathy and renal failure. MATERIAL/METHODS: We evaluated the metabolic effects and tolerability of rosiglitazone as an add-on therapy to insulin in 12 Chinese type 2 diabetic patients (5 males and 7 females) with nephropathy and renal impairment. The mean age of these patients was 65+/-8.3 years, and the mean duration of disease was 16.5+/-8.6 years. The initial daily dosage of rosiglitazone, 2 mg daily, was increased to 4 mg if their fasting plasma glucose concentrations were above 10 mmol/L after 4 weeks. RESULTS: Over a mean period of 15.5 months, HbA1c improved significantly following the addition of rosiglitazone, from 8.57+/-1.42% to 7.48+/-1.3% (p=0.01). There was a trend towards improved lipid profile with this combination therapy, but it was not statistically significant. There was no major adverse events except for minimal weight gain (71.7+/-13.6 kg vs 73.9+/-13.1 kg, p=0.08). CONCLUSIONS: Combination therapy with rosiglitazone and insulin has beneficial metabolic effects and is generally well tolerated in type 2 diabetic patients with nephropathy and mild to moderate renal failure.

Aged↗

PubMed2004

Ethnic differences in the linkage disequilibrium and distribution of single-nucleotide polymorphisms in 35 candidate genes for cardiovascular diseases.

Single-nucleotide polymorphisms (SNPs) are commonly used to study genetics for common diseases and predict pharmacological response. The selection of likely informative SNPs in association studies depends on their allele frequencies and on the linkage disequilibrium (LD) between SNPs, both of which may show interethnic differences. Among three populations consisting of 207 Chinese, 858 French, and 395 Spanish, we compared the allele frequency distributions of 64 intragenic SNPs of 35 candidate genes for cardiovascular diseases. Twenty-eight of these SNPs from 12 genes were also examined for intragenic LD. About 20% of SNPs were restricted to Europeans, being monomorphic in Chinese, among them mostly nonsynonymous coding SNPs and noncoding SNPs. Only 1.6% of SNPs were specific in Chinese, commensurate with the detection of these SNPs almost exclusively in Caucasians. Similarly, these SNPs were more often rare (<0.1 minor allele frequency) in Chinese (44.3%) than in Europeans (31.1%). The variant allele frequencies and intermarker LDs in terms of D' and Delta(2) were highly correlated between French and Spanish populations (r = 0.98-0.99, p < 0.001). However, only moderate correlations of allele frequencies and D' were found between the Chinese and the European populations (r = 0.7 and 0.3, respectively) despite a high correlation of Delta(2) values (r = 0.8). These results suggest that ethnic considerations are important in the selection of SNPs for association studies of candidate genes, as this may affect the power of the study as well as the likelihood of asking relevant questions and getting medically meaningful answers.

Alleles↗

PubMed2004

Effects of obesity on the conversion from normal glucose tolerance to diabetes in Hong Kong Chinese.

OBJECTIVE: To assess the effects of BMI on progression to diabetes in Hong Kong Chinese and to analyze the optimal cutoff for overweight and obesity in Hong Kong Chinese. RESEARCH METHODS AND PROCEDURES: This is a prospective study with a mean follow-up of 2.1 years (median 1.4 years, range 0.9 to 8.4 years). We recruited 172 nondiabetic high-risk subjects, of whom 115 had normal glucose tolerance (NGT) and 57 had impaired glucose tolerance (IGT). BMI and 75-gram oral glucose tolerance tests were assessed at baseline and then at yearly intervals. RESULTS: The crude rates of progression to diabetes for subjects with NGT or IGT were 8.4% and 11.5% per year, respectively. For subjects with NGT, the progression rate to diabetes differed with different BMI ranges. For subjects with NGT and BMI > or = 25 kg/m2, the crude rates of progression to diabetes or glucose intolerance (diabetes or IGT) were 12.5% per year and 14.6% per year, respectively. The corresponding rates for subjects with NGT and BMI > or = 28 kg/m2 were 14.6% and 18.9% per year, respectively. Among subjects with NGT, those with BMI between 25 and 28 kg/m2 had the highest Youden index and likelihood ratio to predict the conversion to diabetes or glucose intolerance. DISCUSSION: Obese subjects with NGT had higher rates of progression to diabetes than nonobese subjects. We recommend redefining BMI cutoffs, with 23 kg/m2 for overweight and 28 kg/m2 for obesity. This definition may be more sensitive to identify at-risk subjects and more specific to identify "patients" for therapeutic management.

Adult↗

PubMed2004

Genome-wide scan for metabolic syndrome and related quantitative traits in Hong Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21-q25.

We conducted autosomal genome scans to map loci for metabolic syndrome (MES) and related traits in the Hong Kong Family Diabetes Study. We selected 55 families with 137 affected members (121 affected relative pairs) for nonparametric linkage analysis on MES. We also selected 179 families with 897 members (2,127 relative pairs) for variance component-based linkage analyses on seven MES-related traits: waist circumference, systolic and diastolic blood pressure (BP), triglyceride, HDL cholesterol, fasting plasma glucose, and insulin resistance index (insulin resistance index by homeostasis model assessment [HOMA%IR]). Analyses revealed three regions that showed suggestive linkage for MES and also showed overlapping signals for metabolic traits: chromosome 1 at 169.5-181.5 cM (logarithm of odds [LOD] = 4.50 for MES, 3.71 for waist circumference, and 1.24 for diastolic BP), chromosome 2 at 44.1-57.3 cM (LOD = 2.22 for MES, 2.07 for fasting plasma glucose, and 1.29 for diastolic BP), and chromosome 16 at 45.2-65.4 cM (LOD = 1.75 for MES, 1.61 for HOMA%IR, and 1.25 for HDL cholesterol). Other regions that showed suggestive linkages included chromosome 5q for diastolic BP; 2q, 3q, 6q, 9q, 10q, and 17q for triglyceride; 12p, 12q, and 22q for HDL-C; and 6q for HOMA%IR. Simulation studies demonstrated genome-wide significant linkage of the chromosome 1 region to both MES and waist circumference (P(genome-wide) = 0.002 and 0.019, respectively). In summary, we have found a susceptibility locus on chromosome 1q21-q25 involved in the pathogenesis of multiple metabolic abnormalities, in particular obesity. Our results confirm the findings of previous studies on diabetes and related phenotypes. We also suggest the locations of other loci that may contribute to the development of MES in Hong Kong Chinese.

Adult↗

PubMed2004

Genome-wide scan for type 2 diabetes loci in Hong Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21-q25.

We conducted an autosomal genome scan to map loci for type 2 diabetes in a Hong Kong Chinese population. We studied 64 families, segregating type 2 diabetes, of which 57 had at least one member with an age at diagnosis of </=40 years. These families included a total of 126 affected sibpairs and 4 other affected relative pairs. Nonparametric linkage analysis revealed seven regions showing nominal evidence for linkage with type 2 diabetes (logarithm of odds [LOD] >0.59, P(pointwise) < 0.05): chromosome 1 at 173.9 cM (LOD = 3.09), chromosome 3 at 26.3 cM (LOD = 1.27), chromosome 4 at 135.3 cM (LOD = 2.63), chromosome 5 at 139.3 cM (LOD = 0.84), chromosome 6 at 178.9 cM (LOD = 1.91), chromosome 12 at 48.7 cM (LOD = 1.99), and chromosome 18 at 28.1 cM (LOD = 1.00). Simulation studies showed genome-wide significant evidence for linkage of the chromosome 1 region (P(genome-wide) = 0.036). We have confirmed the results of previous studies for the presence of a susceptibility locus on chromosome 1q21-q25 (173.9 cM) and suggest the locations of other loci that may contribute to the development of type 2 diabetes in Hong Kong Chinese.

Asian People↗