Multi-ethnic Asian Cohort Research Articles

Clinical management of acute coronary syndrome in Hong Kong

Purpose: Aspirin low responsiveness or “aspirin resistance” has been reported with a prevalence rate of 5.5% to 60% depending on compliance, method, definition and study population. We aimed to assess the prevalence of aspirin responsiveness in a multiethnic Asian cohort planned for percutaneous coronary intervention (PCI). Methods: Of 323 patients screened, 237 patients receiving 75 mg aspirin daily for ≥2 days prior to angiography were recruited in Sarawak General Hospital (Malaysia) between 18/10/2010 and 14/3/2011 with prior written informed consent. Possible noncompliant patients were excluded. Platelet aggregation levels were analysed withmultiple electrode aggregometry (MEA) and expressed as AU*min. 157 patients who had MEA readings with correlation coefficient of ≥0.98 and difference from mean curve of <20% were included for analysis. Patients with MEA of ≥300 AU*min were classified as aspirin low responders. Results: 83.4% of patients were males with mean age of 56.7 years old. 54.1% of patients were Chinese, 23.6% Malays, 22.9% Ibans and 8.9% other ethnic minorities. Median (interquartile range) MEA was 141.0 (86.0) AU*min, 126.0 (74.0) AU*min and 153.0 (98.0) AU*min among Chinese, Malays and Ibans, respectively (p=0.129 Chinese vs. Malays, p=0.777 Chinese vs. Ibans, p=0.115 Malays vs. Ibans). Based on 300 AU*min as cut-off, 10 patients (6.4%) were aspirin low responders, with Ibans accounting for 50%, Chinese 40% and Malays 10%. Median (interquartile range) MEA of responders vs. low responders was 140.0 (78.8) AU*min vs. 439.5 (92.5) AU*min (p=0.001) among Chinese, 125.5 (73.0) AU*min vs. 844.0 (0) AU*min (p=0.092) among Malays and 131.0 (89.0) AU*min vs. 546.0 (174.0) AU*min (p<0.0001) among Ibans. Conclusion: There is a low prevalence of poor aspirin responders in our multiethnic Asian cohort. Aspirin low responsiveness rate was highest among the Iban and Chinese ethnic groups, suggesting a role of ethnicity on aspirin response.

Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients

IntroductionGermline TP53 mutations cause an increased risk to early-onset breast cancer in Li-Fraumeni syndrome (LFS) families and the majority of carriers identified through breast cancer cohorts have LFS or Li-Fraumeni-like (LFL) features. However, in Asia and in many low resource settings, it is challenging to obtain accurate family history and we, therefore, sought to determine whether the presence of early-onset breast cancer is an appropriate selection criteria for germline TP53 testing.MethodsA total of 100 patients with early-onset breast cancer (≤ 35 years) treated at University Malaya Medical Centre between 2003 and 2009, were analyzed for germline mutations in BRCA1, BRCA2 and TP53 by full DNA sequencing. Of the mutations identified, we examined their likely pathogenicity on the basis of prevalence in a case-control cohort, co-segregation analyses and loss of heterozygosity (LOH) in tumor tissues.ResultsWe identified 11 BRCA1 (11%) and 6 BRCA2 (6%) germline carriers among early-onset breast cancer patients. Of the 83 BRCA-negative patients, we identified four exonic variants and three intronic variants in TP53. Of these, two exonic variants are clinically relevant (E346X and p. G334_R335dup6) and two novel missense mutations (A138V and E285K) are likely to be clinically relevant, on the basis of co-segregation and loss of heterozygosity (LOH). Notably, E285K was found in two unrelated individuals and haplotype analyses suggest a founder effect. Two of the three intronic variants are likely benign based on their prevalence in a control population. Clinically relevant TP53 germline mutations were identified in three of the four patients (75%) with a family history of at least two LFS-linked cancers (breast, bone or soft tissue sarcoma, brain tumors or adrenocortical cancer); 1 of the 17 patients (6%) with a family history of breast cancer only, and 1 of the 62 patients (< 2%) with no family history of breast or LFS-linked cancers.ConclusionsOur study reports germline BRCA1, BRCA2 and TP53 mutations are found in early-onset breast cancer patients at 11%, 6% and 5% respectively, suggesting that TP53 mutation screening should be considered for these patients. However, we find that even in low resource Asian settings where family history is poorly reported, germline TP53 mutations are found predominantly among breast cancer patients with a family history of LFS-linked cancers.

Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients

Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients

Prevalence of and Risk Factors for Age-Related Macular Degeneration in a Multiethnic Asian Cohort

To describe the prevalence of and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons. In this population-based study, 3172 persons of Chinese, Malay, and Indian ethnicities 40 years and older were included. Participants underwent comprehensive systemic and ocular examination, retinal photography, and laboratory investigations. Early and late AMD signs were graded from retinal photographs. Age-standardized prevalence estimates were calculated using the 2010 Singapore adult population as the standard population. Association with a range of systemic risk factors was analyzed. Of 3172 participants, AMD was present in 211 subjects. Age-standardized prevalence of AMD was 7.0% in persons 40 years and older. The age-standardized prevalence was similar in all 3 Asian ethnic groups: Chinese, 7.3%; Malay, 7.7%; and Indian, 5.7% (P value = .44). The prevalence increased with age and was higher in men. Of the range of risk factors evaluated, only myopic refractive error (<-0.5 D) was significantly associated with a lower risk for AMD (odds ratio, 0.44; P < .001, compared with emmetropia) in Chinese men. The prevalence of AMD was similar in the 3 major ethnic groups in Asia and comparable with white populations. Myopic refractive error was associated with reduced risk of AMD in Chinese men.

Ethnicity and Heart Failure and Their Epidemiological Profile and Outcomes in a Multi-Ethnic Asian Cohort in Singapore

Ethnicity and Heart Failure and Their Epidemiological Profile and Outcomes in a Multi-Ethnic Asian Cohort in Singapore

Differential Risk for Early Breastfeeding Jaundice in a Multi-ethnic Asian Cohort

To explore the relationship between ethnic origin and mode of feeding with early neonatal jaundice, we examined maternal and neonatal risk factors for hyperbilirubinaemia in a multi-ethnic Asian cohort of healthy term newborns. This is an observational cohort study in a maternity ward serving a multi-ethnic cosmopolitan community. The relationship between hyperbilirubinaemia (bilirubin >or=150 mmol/L before 48 hours to 72 hours after birth), ethnic origin, weight loss after birth, need for phototherapy, and other factors were examined. Bivariate comparisons and binary logistic regression were used to investigate the relationship between hyperbilirubinaemia/phototherapy with maternal and neonatal risk factors. A consecutive group of 1034 neonates (56% Chinese, 24% Indian subcontinent, 9% Malay) with birth weights >or=2500 g was investigated. Overall factors that contributed significantly to hyperbilirubinaemia/phototherapy were gestational age, Chinese ethnic origin, weight loss of >or=7%, vaginal delivery, glucose-6-phosphate-dehydrogenase (G6PD) deficiency, breastfeeding and ABO incompatibility. Chinese neonates who were totally breastfed had a higher risk for jaundice [adjusted odds ratio (OR) = 1.64; 95% confidence intervals (CI), 1.11- 2.44; P <0.014], and phototherapy (adjusted OR = 2.75; 95% CI 1.77-4.27; P <0.001) compared to those supplemented with, or totally formula fed. In contrast, the risk of jaundice for non- Chinese infants did not differ according to the mode of feed. Although weight loss as a whole increased the risk for jaundice (adjusted OR = 1.43; 95%CI, 1.03-1.99; P = 0.031), jaundice in Chinese neonates was not due to ineffective breastfeeding because both Chinese and non-Chinese breastfed infants lost similar weights. Chinese ethnic origin was an independent risk factor for hyperbilirubinaemia and phototherapy. Breastfeeding was not a risk factor for hyperbilirubinaemia/phototherapy in non-Chinese Asian infants.