The dystrophin gene and cognitive function in the general population

The aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included in the analysis. To determine the association between DMD variants and cognitive ability, linear (mixed) modeling with adjustment for age, sex and education was used. Moreover, Sequence Kernel Association Test (SKAT) was used to test the overall association of the rare genetic variants present in the DMD with cognitive traits. Although no DMD variant surpassed the prespecified significance threshold (P<1 × 10⁻⁴), rs147546024:A>G showed strong association (β=1.786, P-value=2.56 × 10⁻⁴) with block-design test in the ERF study, while another variant rs1800273:G>A showed suggestive association (β=−0.465, P-value=0.002) with Mini-Mental State Examination test in the RS. Both variants are highly conserved, although rs147546024:A>G is an intronic variant, whereas rs1800273:G>A is a missense variant in the DMD which has a predicted damaging effect on the protein. Further gene-based analysis of DMD revealed suggestive association (P-values=0.087 and 0.074) with general cognitive ability in both cohorts. In conclusion, both single variant and gene-based analyses suggest the existence of variants in the DMD which may affect cognitive functioning in the general populations.     

Blood pressure and physical fitness in children

The association between physical fitness and blood pressure was studied in 2061 children selected from all fourth graders in 44 elementary schools in the New York City area. Their blood pressure and physical fitness were measured on two consecutive examinations 1 year apart. Systolic and diastolic blood pressure were highest in children with poor physical fitness. The change in physical fitness between the 2 examination years was related to the change in systolic and diastolic blood pressure (i.e., children with a decline in physical fitness showed the largest rise in blood pressure). These observations suggest that the level of systolic and diastolic blood pressure in children is associated with the level of physical fitness. They also indicate that change in blood pressure in childhood may be related to change in physical fitness.     

Low vitamin B6 status in patients with acute myocardial infarction

The vitamin B6 status of 84 patients with acute myocardial infarction was compared with that of 84 control subjects. Pyridoxal and pyridoxal 5'-phosphate (PLP) in plasma and erythrocytes, as well as the basal and total potential activity of the PLP-dependent enzyme aspartate aminotransferase in erythrocytes, were measured for a comprehensive assessment of vitamin B6 status. The mean levels of all vitamin B6 indexes (except pyridoxal) were lower in the patients than in the control subjects. The differences were statistically significant, except for erythrocyte PLP and total potential enzyme activity. The adjusted relative odds of a myocardial infarction for subjects in the lowest quartile of plasma PLP was about 5 times higher when compared with those in the highest quartile (relative odds = 5.2, 95% confidence interval = 1.4 to 18.9). Similar findings were found with the other vitamin B6 indexes. No significant association between infarct size, as estimated by creatine kinase level, and the vitamin B6 indexes was observed.     

Altitude and blood pressure in children

People living at high altitude are generally observed to have lower blood pressure than those residing at sea level. To investigate whether low pO2 or low body weight accounts for this, blood pressure, weight, height and pulse rate were measured in 847 Peruvian children residing at 3500 m and compared to previously collected data in 3924 Dutch children living at sea level. In the two study populations the same protocol for measurement of blood pressure was used by observers who showed no systematic differences in average blood pressure readings during training sessions. Systolic as well as diastolic blood pressure was found to increase with age in both Peruvian and Dutch children. Systolic blood pressure by age was 5-10 mmHg lower in Peruvian boys and girls than in their Dutch counterparts. However, virtually no differences in systolic blood pressure, and to a lesser extent diastolic blood pressure, by body weight or height between Peruvian and Dutch subjects were found. These findings are in agreement with the hypothesis that differences in body weight, rather than in pO2, explain most of the observed differences in blood pressure between children of the same age living at different altitudes.     

C-reactive protein gene haplotypes and risk of coronary heart disease: the Rotterdam Study.

AIMS: C-reactive protein is associated with risk of cardiovascular disease. However, whether C-reactive protein is a marker of severity of cardiovascular disease or actually is involved in its pathogenesis remains unknown. We investigated the relation between C-reactive protein haplotypes, representing the comprehensive variation of the C-reactive protein gene, and coronary heart disease. METHODS AND RESULTS: The Rotterdam Study is a prospective population-based study among men and women aged 55 years and older. C-reactive protein was associated with risk of coronary heart disease, with a multivariable adjusted hazard ratio of 1.9 (95% CI 1.5-2.4) for the highest vs. the lowest quartile. Four C-reactive protein haplotypes were present with overall frequencies of 32.8, 31.7, 29.5, and 5.9%. C-reactive protein serum levels were significantly different according to C-reactive protein haplotypes. C-reactive protein haplotypes were not associated with coronary heart disease. CONCLUSION: Steady-state C-reactive protein serum level is influenced by C-reactive protein gene haplotypes. Although elevated C-reactive protein level has lately been found to be a consistent and relatively strong risk factor for cardiovascular disease, our study does not support that the common variation in the C-reactive protein gene has a large effect on the occurrence of coronary heart disease.     

Ethnicity and social deprivation independently influence metabolic control in children with type 1 diabetes

AIMS/HYPOTHESIS: This study was performed to evaluate the influence of ethnicity and socioeconomic status (SES) on metabolic control in a population-based cohort of children with type 1 diabetes mellitus, and to evaluate whether any relationship between ethnicity and HbA(1c) is mediated by SES. METHODS: We performed a retrospective review of all patients under age 16 years with type 1 diabetes (n = 555) from 1995 to 2005 in the greater Auckland region, New Zealand. Diabetes care variables and HbA(1c) values were collected prospectively, during clinic visits. RESULTS: The mean population HbA(1c) was 8.3 +/- 1.3%. Maori and Pacific patients had poorer metabolic control than their European counterparts (9.1% and 9.3% vs 8.1%, p < 0.001) and higher rates of moderate to severe hypoglycaemia (31.1 and 24.8 vs 14.9 events/100 patient-years, p = 0.03). In multiple linear regression analysis, both ethnicity and SES were independently associated with HbA(1c) (p < 0.001). Other factors associated with higher HbA(1c) level were longer duration of diabetes, higher insulin dose, lower BMI z score and less frequent blood glucose monitoring (p < 0.001). CONCLUSIONS/INTERPRETATION: Both ethnicity and SES independently influenced metabolic control in a large, unselected population of children with type 1 diabetes. Irrespective of SES, Maori and Pacific youth with type 1 diabetes were at greater risk of both moderate to severe hypoglycaemia and long-term complications associated with poor metabolic control.