352 research outputs found
A genome-wide search replicates evidence of a quantitative trait locus for circulating angiotensisn l-converting enzyme (ACE) unlinked to the ACE gene
No full textBackground: angiotensin I-converting enzyme (ACE) plays an important role in cardiovascular homeostasis. There is evidence from different ethnic groups that circulating ACE levels are influenced by a quantitative trait locus (QTL) at the ACE gene on chromosome 17. The finding of significant residual familial correlations in different ethnic groups, after accounting for this QTL, and the finding of support for linkage to a locus on chromosome 4 in Mexican-American families strongly suggest that there may well be QTLs for ACE unlinked to the ACE gene.Methods: a genome-wide panel of microsatellite markers, and a panel of biallelic polymorphisms in the ACE gene were typed in Nigerian families. Single locus models with fixed parameters were used to test for linkage to circulating ACE with and without adjustment for the effects of the ACE gene polymorphisms.Results: strong evidence was found for D17S2193 (Zmax = 3.5); other nearby markers on chromosome 17 also showed modest support. After adjustment for the effects of the ACE gene locus, evidence of "suggestive linkage" to circulating ACE was found for D4S1629 (Zmax = 2.2); this marker is very close to a locus previously shown to be linked to circulating ACE levels in Mexican-American families.Conclusion: in this report we have provided further support for the notion that there are QTLs for ACE unlinked to the ACE gene; our findings for chromosome 4, which appear to replicate the findings of a previous independent study, should be considered strong grounds for a more detailed examination of this region in the search for genes/variants which influence ACE levels.
The poor yields, thus far, in defining the genetic determinants of hypertension risk suggest a need to look beyond simple relationships between genotypes and the ultimate phenotype. In addition to incorporating information on important environmental exposures, a better understanding of the factors which influence the building blocks of the blood pressure homeostatic network is also required. Detailed studies of the genetic determinants of ACE, an important component of the renin-angiotensin system, have the potential to contribute to this strategic objectiv
The relationship among circulating insulin-like growth factor (IGF)-I, IGF-binding proteins-1 and -2, and birth anthropometry: a prospective study
No full textFetal IGF-I is a determinant of birth weight, but whether maternal IGF-I plays a significant role is controversial. We sought to examine the relationships among maternal IGF-I, IGF-binding protein (IGFBP)-1, and IGFBP-2, with maternal and newborn anthropometry, in a cohort of 325 nondiabetic pregnant women of African origin. Blood was collected for IGF-I, IGFBP-1, and IGFBP-2 at 9, 25, and 35 wk gestation and in cord blood at delivery.In the second and third trimesters, maternal IGF-I was significantly correlated (P < 0.005) with maternal body mass index and triceps skinfold thickness. Maternal IGFBP-1 and -2 had an inverse correlation (P < 0.0001), with maternal anthropometry. Maternal IGF-I at 35 wk, and fetal IGF-I by cord blood were significantly correlated with birth weight (P = 0.001 and 0.048, respectively). IGFBP-1 in the third trimester and cord blood were negatively correlated with birth weight (P = 0.012 and 0.002). In multiple regression analyses, maternal IGF-I at 35 wk, fetal IGF-I, maternal weight at the first antenatal visit, gender, and gestational age were significant independent factors in the determination of birth weight. In conclusion, maternal IGF-I levels, especially during late pregnancy, positively influence birth weight
Non-alcoholic fatty liver disease in non-obese subjects of African origin has atypical metabolic characteristics
No full textBackground:
Non-obese non-alcoholic fatty liver disease (NAFLD) is reported in several populations. However, as persons of African origin display unique fat accumulation, insulin resistance and lipid profiles, we investigated fatty liver in non-obese persons of African origin.
Method:
We recruited 78 urban Jamaican volunteers. CT scan was used to estimate liver and abdominal fat; body composition by D-EXA. Fasting blood was collected for lipids, alanine aminotransferase (ALT), adiponectin and fetuin-A. Homeostatic model assessment of insulin resistance (HOMA), whole body insulin sensitivity index (WBISI), insulinogenic index (IGI) and oral disposition index (oDI) were calculated after a 75-g oral glucose tolerance test.
Results:
52% of the participants were male; mean age 28.5±7.8 years and BMI 22.4±3.0 kg/m2 (±SDs). Mean liver attenuation (MLA) and liver: spleen (LS) ratio, both inversely correlated to liver fat, were 62.8±4.3 HU and 1.2±0.1 respectively, and 3.8% of the participants had liver fat >30% (LS ratio<1). In age, sex and BMI-adjusted correlations, MLA was negatively associated with weight (r=-0.30, p=0.009) and height (r=-0.28, p=0.017) and associated with fasting glucose (r=0.23, p=0.05), fasting insulin (r=0.42, p ≤ 0.001) and HOMA-IR (r=0.35, p=0.004). Serum lipids, ALT, adiponectin, fetuin A, WBISI, IGI and oDI were not associated with liver fat.
Conclusions:
In non-obese Afro-Caribbean participants, greater liver fat (lower MLA) was associated with weight and height and lower fasting insulin. Hyperinsulinaemia appears to be influential in the reduction of NAFLD in this group. These findings may be influenced by ethnicity, body size and the method of estimating liver fat
Growth, body composition, and the onset of puberty: longitudinal observations in Afro-Caribbean children
No full textContext: childhood growth and body composition may influence the onset of puberty.Objective: ee examined the effects of birth size, growth rates throughout childhood, and body composition on the onset of puberty in Afro-Caribbean children.Design and setting: this was a longitudinal birth cohort study (the Vulnerable Windows Cohort Study) in Jamaica.Subjects and measurements: the anthropometry (weight, height, skinfold measurements, and waist circumference) of 259 children was measured at birth, at 6 wk, every 3 months to 2 yr, and then every 6 months. Tanner staging for puberty and orchidometry were performed every 6 months starting at approximately age 8 yr. Bioelectrical impedance was done at age 11 yr.Results: In the girls, thelarche, pubarche, and menarche occurred at median ages of 8.8, 9.9, and 12.0 yr, respectively. Pubarche in boys occurred at a median age of 11.3 yr when the median testicular volume was 2.8 ml. Faster weight gain during infancy (age 0–6 months) and childhood, but not birth size, was associated with more advanced puberty (P values <0.05). Fat mass at age 8 yr was associated with more advanced puberty (P values <0.001) in both sexes. At age 11 yr, lean mass, but not fat mass, was associated with more advanced puberty (P values <0.001).Conclusion: these data support the hypothesis that faster growth throughout childhood, especially with fat mass accretion, is associated with more advanced puberty apart from menarche. With the onset of puberty, lean mass accretion significantly increase
Genetic variation on chromosone 6 influences F cell levels in healthy individuals of African descent and HbF levels in sickle cell patients
No full textFetal haemoglobin (HbF) is a major ameliorating factor in sickle cell disease. We investigated if a quantitative trait locus on chromosome 6q23 was significantly associated with HbF and F cell levels in individuals of African descent. Single nucleotide polymorphisms (SNPs) in a 24-kb intergenic region, 33-kb upstream of the HBS1L gene and 80-kb upstream of the MYB gene, were typed in 177 healthy Afro-Caribbean subjects (AC) of approximately 7% European admixture, 631 healthy Afro-Germans (AG, a group of African and German descendents located in rural Jamaica with about 20% European admixture), 87 West African and Afro-Caribbean individuals with sickle cell anaemia (HbSS), as well as 75 Northern Europeans, which served as a contrasting population. Association with a tag SNP for the locus was detected in all four groups (AC, P = 0.005, AG, P = 0.002, HbSS patients, P = 0.019, Europeans, P = 1.5 x 10(-7)). The association signal varied across the interval in the African-descended groups, while it is more uniform in Europeans. The 6q QTL for HbF traits is present in populations of African origin and is also acting in sickle cell anaemia patients. We have started to distinguish effects originating from European and African ancestral populations in our admixed study population
Report on the 2nd World Congress on Fetal Origins of Adult Disease, Brighton, U.K., June 7-10, 2003
No full textIn 1989, reports suggested that the fetal environment, as reflected in birth size, was related to the risk of noncommunicable diseases in adult life. This association was first described for coronary heart disease but rapidly extended to include type 2 diabetes, osteoporosis, and metabolic and endocrine homeostasis. This led to the development of the fetal origins of adult disease paradigm, which resulted in a refocusing of research effort over the next 10 y to consider the lifelong consequences of perinatal influences on chronic diseases. Previously, perinatal influences had largely been seen in terms of teratogenic effects or acute birth injury rather than whether trajectories and responses made during early development had lifelong consequences. Indeed, in developmental biology, it is widely recognized that adaptive plastic responses during early development often have consequences for function in later adulthood. Although the relative importance of this newly recognized set of phenomena to the burden of human disease has been controversial, the research precipitated by those early observations has confirmed their robustness and started to provide a mechanistic basis to this biology. Two world congresses have been held to review progress in this research. Both have been characterized by a unique multidisciplinary attendance ranging from molecular, experimental, and developmental biologists to epidemiologists and health economists
Ethnic differences in F cell levels in Jamaica: a potential tool for identifying new genetic locicontrolling fetal haemoglobin
No full textHigh levels of fetal haemoglobin (HbF) are protective in ?-haemoglobinopathies. The proportion of erythrocytes containing HbF (F-cells, FC) was measured in healthy adults of African and Caucasian ancestry to assess the feasibility of localizing genes for the FC trait using admixture mapping. Participants were Afro-Caribbean (AC) blood donors and residents of a rural enclave with a history of recent German admixture (Afro-German, AG) recruited in Jamaica, and Caucasian Europeans recruited in Jamaica and the UK. FC levels were significantly different between groups (P < 0·001); the geometric mean FC level in the AC sample (n = 176) was 3·75% [95% confidence interval (CI) 3·36–4·18], AG sample (n = 631) was 2·77% (95% CI 2·63–2·92), and among Caucasians (n = 1099) was 3·26% (95% CI 3·13–3·39). After adjustment for age, sex, haemoglobin electrophoresis pattern, and HBG2 genotype, FC levels in the AC group remained significantly different (P < 0·001) from those in the Caucasian and the AG group but the difference between the Caucasian and AG groups became non-significant (P = 0·46) despite substantial differences in average ancestry. The data confirm ethnic differences in FC levels and indicate the potential usefulness of these populations for admixture mapping of genes for FC level
The association of hypothalamic-pituitary-adreanal-axis activity and blood pressure in an Afro-Caribbean population
No full textHyperactivity of the hypothalamic—pituitary—adrenal axi (HPAA) resulting fromfetal programming may play a role in the development of high blood pressure (BP) in black people. We
assessed the diurnal salivary cortisol profile in children with andwithout increased BPand evaluated their mother’s HPAA. In a cross-sectional study, 20Afro-Caribbean children (mean age 9.6 years) with higher blood pressures and 20 children with lower blood pressures were chosen from a prospective study of 569 mothers and children in Jamaica. Daytime salivary cortisol profiles were collected in the children and their mothers. The mothers were also assessed for features of themetabolic syndrome. Children with higher BP had higher mean morning salivary cortisol concentrations than those with lower BP (7.9 S.D. 1.9 vs. 4.5 S.D. 2.4 nmol/l; p = 0.03). Their mothers also had increased morning salivary cortisol concentrations (9.9 S.D. 1.8 vs. 5.5 S.D. 2.5 nmol/l; p = 0.02), but no changes in fasting glucose, insulin, lipids, BP or adiposity. Maternal and offspring cortisol concentrations correlated significantly (r = 0.465, p = 0.004). Maternal cortisol concentrations were
significantly associated with the child’s BP.We conclude that Afro-Caribbean childrenwith higher BP have higher morning salivary cortisol concentrations. The children’s cortisol concentrations correlate significantly with the mother’s cortisol concentrations. These findings suggest that the HPAA may play a role in the development of raised BP in Afro-Caribbean people
The effect of wasting and stunting during severe acute malnutrition in infancy on insulin sensitivity and insulin clearance in adult life
No full textAdults who had non-edematous severe acute malnutrition (SAM) during infancy (i.e., marasmus) have worse glucose tolerance and beta-cell function than survivors of edematous SAM (i.e., kwashiorkor). We hypothesized that wasting and/or stunting in SAM is associated with lower glucose disposal rate (M) and insulin clearance (MCR) in adulthood. We recruited 40 nondiabetic adult SAM survivors (20 marasmus survivors (MS) and 20 kwashiorkor survivors (KS)) and 13 matched community controls. We performed 150-minute hyperinsulinaemic, euglycaemic clamps to estimate M and MCR. We also measured serum adiponectin, anthropometry, and body composition. Data on wasting (weight-for-height) and stunting (height-for-age) were abstracted from the hospital records. Children with marasmus had lower weight-for-height z-scores (WHZ) (-3.8 ± 0.9 vs. -2.2 ± 1.4; P < 0.001) and lower height-for-age z-scores (HAZ) (-4.6 ± 1.1 vs. -3.4 ± 1.5; P = 0.0092) than those with kwashiorkor. As adults, mean age (SD) of participants was 27.2 (8.1) years; BMI was 23.6 (5.0) kg/m2. SAM survivors and controls had similar body composition. MS and KS and controls had similar M (9.1 ± 3.2; 8.7 ± 4.6; 6.9 ± 2.5 mg.kg-1.min-1 respectively; P = 0.3) and MCR. WHZ and HAZ were not associated with M, MCR or adiponectin even after adjusting for body composition. Wasting and stunting during infancy are not associated with insulin sensitivity and insulin clearance in lean, young, adult survivors of SAM. These data are consistent with the finding that glucose intolerance in malnutrition survivors is mostly due to beta-cell dysfunction.</p
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