DESIGN, SETTING AND PARTICIPANTS: We used PCR to determine the size of CTG repeats in 377 individuals not known to be affected by DM and 11 DM1 suspected patients, recruited from a tertiary hospital in Kuala Lumpur. TP-PCR was performed on selected samples, followed by Southern blot hybridisation of PCR amplified fragments to confirm and estimate the size of CTG expansion.
OUTCOME MEASURES: The number of individuals not known to be affected by DM with (CTG)>18 was determined according to ethnic group and as a whole population. The χ2 test was performed to compare the distribution of (CTG)>18 with 12 other populations. Additionally, the accuracy of TP-PCR in detecting CTG expansion in 11 patients with DM1 was determined by comparing the results with that from Southern blot hybridisation.
RESULTS: Of the 754 chromosomes studied, (CTG)>18 frequency of 3.60%, 1.57% and 4.00% in the Malay, Chinese and Indian subpopulations, respectively, was detected, showing similarities to data from Thai, Taiwanese and Kuwaiti populations. We also successfully detected CTG expansions in 9 patients using the TP-PCR method followed by the estimation of CTG expansion size via Southern blot hybridisation.
CONCLUSIONS: The results show a low DM1 prevalence in Malaysia with the possibility of underdiagnosis and demonstrates the feasibility of using a clinical and TP-PCR-based approach for rapid and cost-effective DM1 diagnosis in developing countries.
Methods: : We utilized data among 1020 infants from a mother-offspring cohort, who were Singapore citizens or permanent residents of Chinese, Malay or Indian ethnicity with homogeneous parental ethnic backgrounds, and did not receive chemotherapy, psychotropic drugs or have diabetes mellitus. Ethnicity was self-reported at recruitment and later confirmed using genotype analysis. Subject-specific BMI curves were fitted to infant BMI data using natural cubic splines with random coefficients to account for repeated measures in each child. We estimated characteristics of the child's BMI peak [age and magnitude at peak, average pre-peak velocity (aPPV)]. Systolic (SBP) and diastolic blood pressure (DBP), BMI, sum of skinfolds (SSF) and fat-mass index (FMI) were measured during a follow-up visit at age 48 months. Weighted multivariable linear regression was used to assess the predictors (maternal BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational age and breastfeeding duration) of infant BMI peak and its associations with outcomes at 48 months. Comparisons between ethnicities were tested using Bonferroni post-hoc correction.
Results: : Of 1020 infants, 80.5% were followed up at the 48-month visit. Mean (SD) BMI, SSF and FMI at 48 months were 15.6 (1.8) kg/m 2 , 16.5 (5.3) mm and 3.8 (1.3) kg/m 2 , respectively. Mean (SD) age at peak BMI was 6.0 (1.6) months, with a magnitude of 17.2 (1.4) kg/m 2 and pre-peak velocity of 0.7 (0.3) kg/m 2 /month. Compared with Chinese infants, the peak occurred later in Malay {B [95% confidence interval (CI): 0.64 mo (0.36, 0.92)]} and Indian infants [1.11 mo (0.76, 1.46)] and was lower in magnitude in Indian infants [-0.45 kg/m 2 (-0.69, -0.20)]. Adjusting for maternal education, BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational-age and breastfeeding duration, higher peak and aPPV were associated with greater BMI, SSF and FMI at 48 months. Age at peak was positively associated with BMI at 48 months [0.15 units (0.09, 0.22)], whereas peak magnitude was associated with SBP [0.17 units (0.05, 0.30)] and DBP at 48 months [0.10 units (0.01, 0.22)]. Older age and higher magnitude at peak were associated with increased risk of overweight at 48 months [Relative Risk (95% CI): 1.35 (1.12-1.62) for age; 1.89 (1.60-2.24) for magnitude]. The associations of BMI peak with BMI and SSF at 48 months were stronger in Malay and Indian children than in Chinese children.
Conclusions: : Ethnic-specific differences in BMI peak characteristics, and associations of BMI peak with early childhood cardio-metabolic markers, suggest an important impact of early BMI development on later metabolic outcomes in Asian populations.