Circadian CLOCK gene polymorphisms in relation to sleep patterns and obesity in African Americans: findings from the Jackson heart study.

BACKGROUND: Circadian rhythms regulate key biological processes and the dysregulation of the intrinsic clock mechanism affects sleep patterns and obesity onset. The CLOCK (circadian locomotor output cycles protein kaput) gene encodes a core transcription factor of the molecular circadian clock influencing diverse metabolic pathways, including glucose and lipid homeostasis. The primary objective of this study was to evaluate the associations between CLOCK single nucleotide polymorphisms (SNPs) and body mass index (BMI). We also evaluated the association of SNPs with BMI related factors such as sleep duration and quality, adiponectin and leptin, in 2962 participants (1116 men and 1810 women) from the Jackson Heart Study. Genotype data for the selected 23 CLOCK gene SNPS was obtained by imputation with IMPUTE2 software and reference phase data from the 1000 genome project. Genetic analyses were conducted with PLINK RESULTS: We found a significant association between the CLOCK SNP rs2070062 and sleep duration, participants carriers of the T allele showed significantly shorter sleep duration compared to non-carriers after the adjustment for individual proportions of European ancestry (PEA), socio economic status (SES), body mass index (BMI), alcohol consumption and smoking status that reach the significance threshold after multiple testing correction. In addition, we found nominal associations of the CLOCK SNP rs6853192 with longer sleep duration and the rs6820823, rs3792603 and rs11726609 with BMI. However, these associations did not reach the significance threshold after correction for multiple testing. CONCLUSIONS: In this work, CLOCK gene variants were associated with sleep duration and BMI suggesting that the effects of these polymorphisms on circadian rhythmicity may affect sleep duration and body weight regulation in Africans Americans.

Obstructive sleep apnea risk and leukocyte telomere length in African Americans from the MH-GRID study.

PURPOSE: Shorter telomere length and obstructive sleep apnea are associated with increased oxidative stress and chronic inflammation, which are both considered leading causes of age-related diseases. Different forms of sleep disordered breathing have been linked to telomere length although their relationship remains uncertain. The purpose of this study was to explore the associations between the risk of obstructive sleep apnea and telomere length in African Americans. METHODS: The analysis included 184 women and 122 men aged 30-55 years from the Morehouse School of Medicine Study. Relative TL (T/S ratio) was measured from peripheral blood leukocytes using quantitative real-time polymerase chain reaction. The Berlin questionnaire was used for OSA risk assessments. Multivariable linear regression models were used to examine the associations between OSA risk and LTL. RESULTS: We observed that LTL varied by OSA risk in women (0.532 ± 0.006 vs. 0.569 ± 0.008) (p = 0.04). Multiple linear regression analysis confirmed that women at higher risk for OSA presented shorter LTL compared to those at lower risk, independent of age, income, education, obesity, smoking, alcohol consumption, and hypertension. These differences were not observed in men. CONCLUSIONS: Our findings suggest that OSA risk may contribute to the acceleration of cellular aging processes through telomere shortening.

Vitamin D Receptor Gene Polymorphisms Are Associated with Abdominal Visceral Adipose Tissue Volume and Serum Adipokine Concentrations but Not with Body Mass Index or Waist Circumference in African Americans: The Jackson Heart Study.

BACKGROUND: The biological actions of vitamin D are mediated through the vitamin D receptor (VDR). Single-nucleotide polymorphisms (SNPs) in the VDR gene have been previously associated with adiposity traits. However, to our knowledge, few studies have included direct measures of adiposity and adipokine concentrations. OBJECTIVE: We examined the association of tagging SNPs in the VDR gene with multiple adiposity measures, including waist circumference (WC), body mass index (BMI), body fat percentage, subcutaneous and visceral adipose tissue (VAT) volume, and serum adipokine (adiponectin and leptin) concentrations in adult African Americans (AAs). METHODS: Data from 3020 participants (61.9% women; mean age, 54.6 y) from the Jackson Heart Study were used for this analysis. Forty-five tag SNPs were chosen with the use of genotype data from the International HapMap project. We used linear regression to test the associations of imputed VDR SNPs with each of the traits, adjusted for age, sex, educational status, physical activity, smoking, alcohol intake, serum vitamin D concentration, European ancestry, and multiple testing. RESULTS: The G allele of the SNP rs4328262 remained associated with increased VAT volume after multiple testing correction (ß = 45.7; P < 0.001). The A allele of another SNP (rs11574070) was nominally associated with body fat percentage (ß = 0.96; P = 0.002). None of the VDR SNPs analyzed showed any link with WC or BMI. The A allele of rs2228570 (ß = 0.08; P = 0.001) for men and the T allele of rs2853563 (ß = 0.04; P < 0.001) for women remained positively associated with serum adiponectin concentrations after multiple testing correction. CONCLUSION: Although we did not find any association for anthropometric measures, we did observe associations of VDR variants with serum adipokines and with the more metabolically active fat, VAT. Therefore, our findings demonstrate a possible role of VDR variants in regulating adipose tissue activity and adiposity among AAs.

Associations between Vitamin D and Cardiovascular Disease Risk Factors in African Americans Are Partly Explained by Circulating Adipokines and C-Reactive Protein: The Jackson Heart Study.

BACKGROUND: Although it is recognized that vitamin D deficiency is associated with cardiovascular disease (CVD) risk factors, and is more common in African Americans (AAs), the pathologic mechanisms by which vitamin D may influence these risk factors are poorly understood. OBJECTIVES: We explored the association between vitamin D status, as reflected by serum 25-hydroxyvitamin D [25(OH)D] concentrations, and CVD risk factors including mean arterial pressure (MAP), fasting plasma glucose (FPG), plasma HDL cholesterol, and waist circumference (WC) in adult AAs. We also tested whether plasma C-reactive protein (CRP), adipokines (adiponectin and leptin), and aldosterone mediated the associations between 25(OH)D and these risk factors. METHODS: Data on 4010 (63.8% women; mean age: 54.0 y) individuals from the Jackson Heart Study were analyzed. Multivariable linear regression models were used to examine the associations of 25(OH)D with CVD risk factors. We used path analysis and bootstrapping methods to quantify and test the share of these associations that was statistically explained by each of the mediators by decomposing the associations into direct and indirect effects. RESULTS: Serum 25(OH)D concentrations were inversely associated with WC, FPG, and MAP and were positively associated with HDL cholesterol in multivariable analysis. A nearly 20% effect of 25(OH)D on MAP was masked by aldosterone (total indirect effect: ß = 0.01, P < 0.05). Approximately 23% of the effect of 25(OH)D on WC (ß = -0.03, P < 0.05) and ∼9% of the effect of 25(OH)D on FPG (ß = -0.02, P < 0.05) were mediated through CRP, adiponectin, and leptin together. A 23% share of the association between 25(OH)D and HDL cholesterol was mediated by adiponectin alone (ß = 0.03, P < 0.05). CONCLUSIONS: Our findings suggest that the associations between vitamin D status and CVD risk factors in AAs are partially mediated through circulating adipokines and CRP. More evidence, however, is required from longitudinal and randomized controlled studies to validate our findings.

Genetic ancestry is associated with measures of subclinical atherosclerosis in African Americans: the Jackson Heart Study.

OBJECTIVE: To determine whether genetic ancestry was associated with subclinical atherosclerosis measures after adjustment for traditional cardiovascular disease risk factors, inflammatory marker, socioeconomic status, and psychosocial factors in a large admixed African American population. APPROACH AND RESULTS: Participants were drawn from the Jackson Heart Study. Participant's percent of European ancestry (PEA) was estimated based on 1747 genetic markers using HAPMIX. Association of PEA with peripheral arterial disease and common carotid intima-media thickness were investigated among 2168 participants and with coronary artery calcification >0 and abdominal aortic calcification >0 among 1139 participants. The associations were evaluated using multivariable regression models. Our results showed that a 1 SD increase in PEA was associated with a lower peripheral arterial disease prevalence after adjusting for age and sex (prevalence ratio=0.90 [95% CI, 0.82-0.99]; P=0.036). Adjustments for traditional cardiovascular disease risk factors, socioeconomic status, and psychosocial factors attenuated this association (prevalence ratio=0.91 [0.82-1.00]; P=0.046). There was also a nonlinear association between PEA and coronary artery calcification and abdominal aortic calcification. The lowest PEA was associated with a lower coronary artery calcification (prevalence ratio=0.75 [0.58-0.96]; P=0.022) and a lower abdominal aortic calcification [prevalence ratio=0.80 [0.67-0.96]; P=0.016) compared with the reference group (10th-90th percentile) after adjusting for traditional cardiovascular disease risk factors, inflammatory marker, socioeconomic status, and psychosocial factors. However, we found no significant association between PEA and common carotid intima-media thickness. CONCLUSIONS: Overall, our findings indicate that genetic ancestry was associated with subclinical atherosclerosis, suggesting unmeasured risk factors and interactions with genetic factors might contribute to the distribution of subclinical atherosclerosis among African Americans.

Sex-related differences in the association of ghrelin levels with obesity in adolescents.

BACKGROUND: The utility of ghrelin as a biomarker may be different depending on gender. The aim of this study was to assess ghrelin levels in a population-based sample of adolescents, and to evaluate their association with obesity and obesity-related parameters depending on sex. METHODS: The studied population included 601 randomly selected 14-to 16-year-old children. Anthropometrical data were measured and body mass index (BMI) and waist to hip ratio calculated. Body composition was assessed using an impedance body composition analyzer. Total serum ghrelin levels were determined using a multiplexed bead immunoassay. Serum leptin and adiponectin levels were determined by ELISA and insulin by RIA. RESULTS: Ghrelin levels were significantly higher in girls than in boys. Serum ghrelin concentrations were significantly lower (p<0.01) in obese than in normal weight (NW) girls, but showed no differences by weight category in boys. Ghrelin showed a significant negative relationship with waist circumference (WC), waist to hip ratio and fat mass (p<0.05) in both genders, and with weight and BMI (p<0.01) in girls, and insulin (p<0.01) and HOMA (p<0.05) in boys. Ghrelin also correlated negatively with leptin levels in girls (p<0.01). CONCLUSIONS: Our study describes serum ghrelin levels in adolescents, showing a sexual dimorphism in ghrelin levels in these 14-to 16-year-old children, and a different association of ghrelin levels with obesity by gender that suggests a different appetite and energy expenditure control depending on sex at this age.

Association of adiponectin and socioeconomic status in African American men and women: the Jackson heart study.

BACKGROUND: Recent emphasis has been placed on elucidating the biologic mechanism linking socioeconomic status (SES) to cardiovascular disease (CVD). Positive associations of inflammatory biomarkers provide evidence suggestive of a biologic pathway by which SES may predispose to CVD. African Americans have disproportionately lower SES and have a higher prevalence of CVD risk factors compared to most ethnic/racial groups. Adiponectin (an anti-inflammatory marker) is also lower. The objective of this study was to assess the association of adiponectin with SES among African American men and women using the Jackson Heart Study. METHODS: Study sample included 4340 participants. Linear regression was performed separately by SES and stratified by sex. Annual household income and level of education was used as proxies for SES. Crude, age, health behavior and health status adjusted models were analyzed. The main outcome was log-transformed adiponectin. RESULTS: Men in the lowest income group had significantly higher adiponectin than those in the highest income group in the fully adjusted model (ß/standard error [se], p value = .16/.08, p = .0008. Men with < high school level of education had significantly higher adiponectin in the crude and age adjusted models than those with ≥ college degree (.25/.05, p < .0001; .14/.05/ p = .005, respectively). Women with some college or vocational training in the crude and age adjusted models had lower adiponectin compared to women with ≥ college degree (-.09/.03, p = .004; -.06/.03, p = .04, respectively). CONCLUSION: Findings suggest a potential inverse biologic pathway between annual household income and adiponectin among African American men. There was no such finding among women. Findings suggest interventions should be targeted for higher SES African American men to improve adiponectin levels.

Gender-specific associations between ADIPOQ gene polymorphisms and adiponectin levels and obesity in the Jackson Heart Study cohort.

BACKGROUND: Despite the important role of adiponectin in regulating general metabolic homeostasis, analysis of genetic determinants of adiponectin and the related cardio-metabolic traits in African American population has been limited and inconsistent. Considering the high genetic admixture of African Americans and thus the important population stratification that may confound the genetic-trait associations, the objective of this work was to perform a comprehensive analysis of the associations between ADIPOQ variants and adiponectin levels and obesity phenotypes in a large African American population from the Jackson Heart Study (JHS) cohort. METHODS: Genotype data was available for 2968 JHS participants (1131men; 1837women). Single Nucleotide Polymorphisms (SNPs) were selected by a Tag-SNP Approach and literature review. The genotype imputation was performed using IMPUTE2 software and reference phased data from the 1000G project. PLINK software was used for the genetic analysis. Plasma specimens were analyzed by ELISA for adiponectin levels. All analyses were controlled for population stratification assessed by Individual Proportions of European Ancestry (PEA) estimates calculated in HAPMIX using ancestry informative markers (AIMs). RESULTS: We found a gender-dependent association of some ADIPOQ variants and adiponectin levels. In women four of the studied polymorphisms (rs6444174, rs16861205, rs1403697, rs7641507) were associated with adiponectin levels after Bonferroni correction and controlling for the percentage of PEA, age, annual household income and smoking. These results were consistent with the haplotype analysis. The association between the rs12495941 variant and obesity is modulated by the PEA, so that the relationship between the G allele and a higher incidence of obesity was present in those individuals within the lower PEA group. In addition we found an effect modification of obesity on the association between the ADIPOQ rs6444174 SNP and BMI so that the presence of the T allele was negatively and significantly associated with BMI only in participants with a normal weight. CONCLUSIONS: In this large African American cohort, ADIPOQ variants were associated with adiponectin levels in a gender-dependent manner and the relationship of some of these variants with obesity and BMI was modulated by the PEA and obesity status respectively. This suggests that the effects of these polymorphisms on adiponectin and obesity phenotypes are subject to a strong interaction with genetic and environmental factors in African American population.

Association of ADIPOQ gene with type 2 diabetes and related phenotypes in African American men and women: the Jackson Heart Study.

BACKGROUND: African Americans experience disproportionately higher prevalence of type 2 diabetes and related risk factors. Little research has been done on the association of ADIPOQ gene on type 2 diabetes, plasma adiponectin, blood glucose, HOMA-IR and body mass index (BMI) in African Americans. The objective of our research was to assess such associations with selected SNPs. The study included a sample of 3,020 men and women from the Jackson Heart Study who had ADIPOQ genotyping information. Unadjusted and adjusted regression models with covariates were used with type 2 diabetes and related phenotypes as the outcome stratified by sex. RESULTS: There was no association between selected ADIPOQ SNPs with type 2 diabetes, blood glucose, or BMI in men or women. There was a significant association between variant rs16861205 and lower adiponectin in women with minor allele A in the fully adjusted model (ß(SE) p = -.13(0.05), 0.003). There was also a significant association with variant rs7627128 and lower HOMA-IR among men with minor allele A in the fully adjusted model (ß(SE) p = -0.74(0.20), 0.0002). CONCLUSIONS: These findings represent new insights regarding the association of ADIPOQ gene and type 2 diabetes and related phenotypes in African American men and women.

Association of adiponectin with type 2 diabetes and hypertension in African American men and women: the Jackson Heart Study.

BACKGROUND: Adiponectin is a biomarker that is associated with type 2 diabetes and hypertension. Lower circulating level is a risk factor. Higher levels are protective. African Americans have a higher prevalence of type 2 diabetes and hypertension and lower levels of adiponectin when compared to other racial/ethnic groups. Little is known about the association of adiponectin on these health outcomes among African Americans. The purpose of the study was to assess the association of adiponectin on type 2 diabetes and hypertension likelihood among African American men and women in the Jackson Heart Study. METHODS: Separate multivariate logistic regressions were conducted stratified by sex based on cross-sectional data with type 2 diabetes and hypertension as the outcomes. Adiponectin was divided into four quartiles with the highest quartile as the reference. Data was collected from 2000-2004 on 3,663 participants. Data analysis was conducted in calendar year 2014. Two- tailed P < .05 was established as level of significance. RESULTS: In the adjusted multivariate models, adiponectin level was inversely associated with type 2 diabetes among women (odds ratio [OR], 95% confidence interval [CI] = 1.47, [1.02, 2.11], P = .04). There was no association among men. Women with the lowest level of adiponectin were less likely to be hypertensive (OR, 95% CI = 0.66, [0.46, 0.95], p = .02). There was no association among men. CONCLUSION: Findings reveal differential associations between levels of adiponectin with type 2 diabetes and hypertension likelihood among African American women. More research is needed to elucidate this differential association.

Metastatic lesions with and without interleukin-18-dependent genes in advanced-stage melanoma patients.

IL-18 is an immune-stimulating cytokine that promotes experimental melanoma metastasis via vascular endothelial growth factor (VEGF)-induced very late antigen (VLA)-4. We studied genes associated with the ability of melanoma cells to allow metastasis under IL-18 effects, and we verified their expression in metastatic lesions from patients with melanoma. Human melanoma cell lines with and without the IL-18 receptor (IL-18R)/VEGF/VLA-4-expressing phenotype were identified, and their metastatic potential was studied in nude mice. RNA from untreated and IL-18-treated melanoma phenotypes was hybridized to a cDNA microarray, and their signature genes were studied. RNA from primary and metastatic lesions from patients with melanoma was hybridized to a cDNA microarray to identify lesions with the transcript patterns of melanoma cells with and without the IL-18R/VEGF/VLA-4 phenotype. IL-18R/VEGF/VLA-4-expressing A375 and 1182 melanoma cells produced a higher metastasis number than 526 and 624.28 melanoma cells, not using this prometastatic pathway. Melanoma cells with and without the IL-18R/VEGF/VLA-4 phenotype had distinct transcript patterns. However, the type I transcriptional cluster, including cutaneous and lymph node metastases, but not the type II cluster, not including cutaneous metastases, had signature genes from IL-18-treated melanoma cells with, but not without, the IL-18R/VEGF/VLA-4 phenotype. Metastatic melanoma lesions with and without IL-18-dependent genes were identified, suggesting that melanoma metastasis developed via inflammation-dependent and inflammation-independent mechanisms. Signature genes from melanomas with and without the IL-18R/VEGF/VLA-4 phenotype may serve as diagnostic biomarkers of melanoma predisposition to prometastatic effects of IL-18.

Association of resistin polymorphisms with resistin levels and lipid profile in children.

Previous research has found a correlation between resistin and lipid level variations. Polymorphisms in the resistin gene (RETN) could be involved in this relationship, but the results of the different studies are contradictory. The aim of this study was to examine the association between resistin and lipid levels, and to determine whether resistin polymorphisms are associated with resistin levels and lipid profile in prepubertal children and adolescents. The single nucleotide polymorphisms (SNPs) rs1862513 and rs10401670 were analyzed in 442 randomly selected 6- to 8-year-old children and 827 children aged 12-16 years. Anthropometric data were recorded. Lipid profile was determined using standard methods. Serum resistin levels were measured using a multiplexed bead immunoassay. Resistin polymorphisms were determined by TaqMan(®) allelic discrimination assays. A relationship was found between serum levels of resistin and the SNP rs10401670 in 6- to 8-year-old boys. SNP rs10401670 was also related to TC and LDL-cholesterol in 12- to 16-year-old boys and to HDL-C in 12- to 16-year-old girls. SNP rs1862513 was not related to any of the studied variables. Serum resistin levels were significantly and negatively associated with ApoAI levels in 12- to 16-year-old girls. A SNP in the 3'UTR region of RETN (rs10401670) is associated with resistin levels and lipid profile in children, showing different associations depending on age and gender.

Influence of the interaction between the adiponectin G276T polymorphism and body mass index on lipid levels in healthy children.

Adiponectin is an adipose tissue-specific hormone which is inversely associated with metabolic alterations related to atherosclerosis. Polymorphisms in the adiponectin gene (AdipoQ) have been related to low adiponectin levels as well as several cardiovascular risk factors, but this association remains controversial. In our study we investigated the relationship between the AdipoQ T45G (rs: 2241766) and G276T (rs: 1501299) polymorphisms and adiponectin concentrations, blood pressure, and lipid and insulin levels, in a population-based sample of 12- to 16-year-old children. The study included 815 healthy Spanish children (388 boys and 427 girls). Plasma glucose and lipid levels were determined by standard methods. Insulin concentrations were measured by RIA, and serum adiponectin levels were determined by ELISA. The AdipoQ T45G and AdipoQ G276T polymorphisms were determined by TaqMan(®) allelic discrimination assays. ANOVA or t test allowed for comparison of the studied parameters across genotypes or genotype groups, respectively. A linear regression analysis was performed to examine the independent relationships of the lipid variables with BMI (body mass index), AdipoQ G276T polymorphism and the interaction between the two. When independently comparing the effect of these polymorphisms in normal-weight and overweight children, we observed that overweight boys carriers of the minor allele T had significantly lower TC, LDL-C and apo A-I levels than non-carriers, but these differences were not apparent in normal-weight boys. Furthermore, linear regression analysis demonstrated that interaction between the BMI and the AdipoQ G276T polymorphism is a significant factor explaining the variations of TC and LDL-C levels. To our knowledge, this is the first study to report an association between the AdipoQ G276T polymorphism and lipid levels in overweight boys alone, thereby suggesting that the influence of the AdipoQ polymorphisms on cardiovascular risk factors may be dependent on BMI.

Influence of the leptin G-2548A polymorphism on leptin levels and anthropometric measurements in healthy Spanish adolescents.

Polymorphisms in the leptin gene (LEP) have been associated with leptin levels and obesity in some studies in adults though this link has scarcely been investigated in children. In our study, we examined the relationship of the LEP G-2548A polymorphism with leptin levels, anthropometric variables and body composition in a population-based sample of pubescent children. Our study included 880 healthy schoolchildren (419 males and 461 females), 12-16 years of age. Plasma leptin levels were determined by ELISA. The LEP polymorphism was determined by allelic discrimination TaqMan assay. Male carriers of the AA genotype had significantly lower plasma leptin levels than GA (p < 0.008) and GG (p < 0.001) carriers and significantly lower mean hip circumference (HC) values than GG carriers (p = 0.04). In girls, leptin levels were also lower in A-allele carriers than in GG carriers, and BMI and HC were significantly lower in AA carriers as compared with GG carriers. In addition, the frequency of the A allele was significantly lower (chi(2): 4.58, p = 0.032) in the OW-obese than in the NW group. In conclusion, the LEP G-2548A polymorphism is associated with variations in leptin levels, BMI and HC in Spanish pubertal children, and evidence suggests a link between the G allele and presence of overweight in girls.

Sex hormone-binding globulin levels and metabolic syndrome and its features in adolescents.

BACKGROUND: Low levels of sex hormone-binding globulin (SHBG) are associated with obesity, insulin resistance, and metabolic syndrome (MS) in men and women, and it has been suggested that SHBG could be a useful marker for MS risk. OBJECTIVE: The aim of this study was to analyze the relationship of SHBG levels with MS and its components in Spanish adolescents. METHODS: The sample population of this cross-sectional study was comprised of 386 male and 429 female adolescents, aged 12-16 yr. Anthropometric parameters and blood pressure (BP) were measured. Total cholesterol, high-density lipoprotein (HDL)-cholesterol, insulin, glucose, and SHBG levels were determined. The pediatric International Diabetes Federation (IDF) definition was used to classify adolescents for MS. RESULTS: SHBG levels were lower in adolescents with MS or with some MS features. More than 90% of the abdominally obese adolescents were in the lowest and medium SHBG tertiles. In girls, BP was significantly higher in the lowest SHBG tertile than in the two others, whereas in boys BP levels were significantly higher in the lowest and medium tertiles than in the highest one. Insulin levels and homeostasis model assessment (HOMA) index were also significantly higher in the lowest SHBG tertile than in the two others. CONCLUSIONS: The associations of SHBG with MS and its components, such as abdominal obesity, high BP or insulin levels, are already present in normal adolescents. This may suggest the possibility of using SHBG levels as a biomarker for MS risk in adolescents as well as adults.

Leptin and adiponectin levels in pubertal children: relationship with anthropometric variables and body composition.

BACKGROUND: Adipocytokines play an important role in controlling energy homeostasis, and in various metabolic processes related to obesity. The aim of this study was to describe serum leptin and adiponectin concentrations in a sample of pubertal Spanish children and to evaluate their association with anthropometric parameters and body composition. METHODS: The study included 833 pubertal boys and girls. Serum leptin and adiponectin concentrations were determined by ELISA. RESULTS: Leptin concentrations were significantly higher (p<0.0001) in obese or overweight (OW) children compared with children with normal weight (NW). Adiponectin was significantly lower (p<0.01) in obese or OW girls compared with girls of NW, although these findings were not the same for boys. Weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist to hip ratio were significantly correlated (p<0.01) with leptin concentrations in both genders. Correlation of leptin with fat mass and % fat mass was strong, particularly in boys. The association of adiponectin concentrations with anthropometric variables was weaker in both genders. No significant correlations were found between adiponectin concentrations and fat mass or % fat mass. CONCLUSIONS: In summary, our study showed that, in pubertal children, leptin is related to weight, BMI, WC and HC and correlates even more strongly with % fat mass. However, adiponectin was weakly related to anthropometric variables and was not correlated with body fat.

Opposite Association of Adropin Concentrations with Obesity in Prepubertal Children Compared with Adolescents.

OBJECTIVE: The aim of this study was to evaluate the association between obesity and plasma adropin levels in two cohorts of children at two different ages. METHODS: Adropin concentrations were measured in 71 prepubertal and 41 pubertal children with obesity and their age- and sex-matched normal weight counterparts (69 prepubertal and 42 pubertal children). Information was available in these children on insulin levels, lipid profile, and leptin levels. Adropin levels were measured by using a commercial enzyme-linked immunosorbent assay kit. RESULTS: Plasma adropin levels were significantly higher (P < 0.001) in prepubertal than pubertal children. Adropin concentrations were significantly higher (P < 0.001) in prepubertal girls than in prepubertal boys but significantly lower (P < 0.001) in pubertal girls than in pubertal boys. Prepubertal boys and girls with obesity had significantly higher adropin levels (P < 0.001) than their normal weight counterparts. In contrast, no differences in adropin levels were observed in pubertal children when comparing children with obesity and normal weight boys and girls. CONCLUSIONS: An important decrease in adropin levels in pubertal children compared with prepubertal children was shown as well as a differing association of adropin with obesity depending on age. These findings suggest a possible relationship between adropin levels and centrally regulated sex hormones involved in pubertal development.

Fat intake influences the effect of the hepatic lipase C-514T polymorphism on HDL-cholesterol levels in children.

Polymorphisms in the hepatic lipase gene have been associated with variability in plasma HDL-C concentrations, but contradictory results have been reported regarding the effect of diet on this association in adults. In our study, we examined whether dietary fat intake modified the association between lipid levels and the C-514T polymorphism in the hepatic lipase gene (LIPC C-514T) in prepubescent children. The LIPC C-514T polymorphism was determined by PCR and restriction analysis in 1260 healthy school children, aged 6-8. Information on the children's nutrient intake was obtained by means of a validated food frequency questionnaire. We found that regardless of gender, carriers of the minor allele had significantly higher apo A-I levels compared to noncarrier subjects. The effect of the polymorphism, however, was modified by dietary fat intake. In boys, the presence of the LIPC C-514T polymorphism was associated with significantly higher HDL-C among children within the highest tertiles of total, saturated, monounsaturated, or polyunsaturated fat intake. Apo A-I levels were significantly higher in carriers of the LIPC C-514T polymorphism, but only among boys who consumed high total as well as monounsaturated fat and among girls who consumed high total, saturated, monounsaturated, and polyunsaturated fat. Our data show that dietary fat intake modifies the effect of the LIPC C-514T polymorphism on plasma HDL-C and apo A-I levels in prepubescent children, being associated with higher levels of HDL-C and apo A-I only when fat intake is high. This significant gene-nutrient interaction could help to explain inter-individual variations in the plasma lipid response to fat intake.

Less Than Ideal Cardiovascular Health Is Associated With Shorter Leukocyte Telomere Length: The National Health and Nutrition Examination Surveys, 1999-2002.

BACKGROUND: The associations between individual cardiovascular disease risk factors and leukocyte telomere length (LTL) have been inconclusive. We investigated the association between LTL and overall cardiovascular health (CVH) as defined by the American Heart Association and whether the association is modified by sex and race/ethnicity. METHODS AND RESULTS: We included 5194 adults (aged ≥20) from the National Health and Nutrition Examination Survey 1999-2002. CVH was defined as a composite score of the 7 metrics (smoking, physical activity, diet, body mass index, blood pressure, total cholesterol, and fasting blood glucose) and categorized as "poor," "intermediate," and "ideal." LTL was assayed from whole blood using the quantitative polymerase chain reaction method relative to standard reference DNA. Multivariable linear regression models were used to estimate the association between CVH and log-transformed LTL. We found strong graded association between CVH and LTL in the overall sample, with evidence of dose-response relationship (P for trend=0.013). Individuals with poor and intermediate CVH had significantly shorter LTL than individuals with ideal CVH (-3.4% [95% CI=-6.0%, -0.8%] and -2.4% [-4.4%, -0.3%], respectively), after adjustment for demographic variables, socioeconomic status, and C-reactive protein. The association was stronger in women (-6.6% [-10.2%, -2.9%] for poor vs ideal CVH) and non-Hispanic whites (-4.3% [-7.1%, -1.4%] for poor vs ideal CVH). CONCLUSIONS: The findings suggest that less-than-ideal CVH is associated with shorter LTL, but this association varies by sex and race/ethnicity. Future longitudinal research is needed to elucidate the mechanisms that underlie the association between CVH and LTL.

Differentially conserved transcriptomic response to adversity related to self-rated health in the multi-ethnic study of atherosclerosis.

Self-rated health (SRH) is considered a strong indicator of well-being and clinical health status and has been linked to inflammatory markers. The objective of this work was to examine how self-rated physical health (SRPH) and mental health (SRMH) influence the immune system through the regulation of a stress-related gene expression profile known as the 'conserved transcriptional response to adversity' (CTRA), which involves the up-regulation of pro-inflammatory genes and down-regulation of genes involved in type I interferon (IFN) response and antibody synthesis. CTRA expression data were derived from genome-wide transcriptional data on purified monocytes in 1264 adult participants from the multi-ethnic study of atherosclerosis. SRPH and SRMH were assessed through the SF-12 questionnaire. Multiple linear regression models were used to determine the association between the composite score of the CTRA subsets and SRPH and SRMH. Higher scores of SRPH and SRMH were associated with an increased expression of the overall CTRA profile. The individual gene subsets analysis did not reveal an increased expression of pro-inflammatory genes in persons with lower scores of SRH. However, we observed that higher scores of SRPH positively modulate the immune response through the up-regulation of both type I interferon response and antibody synthesis-related genes, while better scores of SRMH were associated with a down-regulation of genes involved in antibody synthesis. The significant association between SRH and a gene expression profile related to type I IFN response and antibody synthesis suggests that SRH may be linked to the immunocompetence status. Impact statement In this work, we evaluated for the first time how self-rated mental (SRMH) and physical health (SRPH) influence the immune response at the molecular level in a large multi-ethnic cohort. We observed that both SRMH and SRPH are related to immunocompetence status. These findings indicated that the link between how we perceive our health and poorer health outcomes could be explained by alterations in the immune response by shifting the expression of genes related to the type I IFN response and antibody synthesis.