Ruihua Xu

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

BackgroundDespite 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.MethodsGenotype 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).ResultsWe 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.ConclusionsIn 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.

Prevalence, associated factors and heritabilities of metabolic syndrome and its individual components in African Americans: the Jackson Heart Study

Objective Both environmental and genetic factors play important roles in the development of metabolic syndrome (MetS). Studies about its associated factors and genetic contribution in African Americans (AA) are sparse. Our aim was to report the prevalence, associated factors and heritability estimates of MetS and its components in AA men and women. Participants and setting Data of this cross-sectional study come from a large community-based Jackson Heart Study (JHS). We analysed a total of 5227 participants, of whom 1636 from 281 families were part of a family study subset of JHS. Methods Participants were classified as having MetS according to the Adult Treatment Panel III criteria. Multiple logistic regression analysis was performed to isolate independently associated factors of MetS (n=5227). Heritability was estimated from the family study subset using variance component methods (n=1636). Results About 27% of men and 40% of women had MetS. For men, associated factors with having MetS were older age, lower physical activity, higher body mass index, and higher homocysteine and adiponectin levels (p<0.05 for all). For women, in addition to all these, lower education, current smoking and higher stress were also significant (p<0.05 for all). After adjusting for covariates, the heritability of MetS was 32% (p<0.001). Heritability ranged from 14 to 45% among its individual components. Relatively higher heritability was estimated for waist circumference (45%), high density lipoprotein-cholesterol (43%) and triglycerides (42%). Heritability of systolic blood pressure (BP), diastolic BP and fasting blood glucose was 16%, 15% and 14%, respectively. Conclusions Stress and low education were associated with having MetS in AA women, but not in men. Higher heritability estimates for lipids and waist circumference support the hypothesis of lipid metabolism playing a central role in the development of MetS and encourage additional efforts to identify the underlying susceptibility genes for this syndrome in AA.

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.

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 (β = 45.7; P < 0.001). The A allele of another SNP (rs11574070) was nominally associated with body fat percentage (β = 0.96; P = 0.002). None of the VDR SNPs analyzed showed any link with WC or BMI. The A allele of rs2228570 (β = 0.08; P = 0.001) for men and the T allele of rs2853563 (β = 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.

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

BackgroundAdiponectin 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.MethodsSeparate 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.ResultsIn 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.ConclusionFindings 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.

Parent-offspring association of metabolic syndrome in the Framingham Heart Study

BackgroundMetabolic syndrome (MetS) is a clustering of five metabolic risk factors including abdominal obesity, elevated blood pressure, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), and impaired fasting glucose. Few studies have fully reported the strength of clustering of these risk factors in a parent-offspring relationship. This analysis describes the associations between parents and their adult offspring in regard to MetS. It also estimates the association between each risk factor in parents and the presence of MetS in their offspring.MethodsWe analyzed data for 1193 offspring (565 sons, and 628 daughters) from the Framingham Offspring Study who attended examinations 5, 6, and 7. Information about their parents was collected from examinations 13, 14 and 15 of the Framingham Original Cohort study. We used pedigree file to combine parental and offspring’s data. Participants were classified as having the MetS according to the Adult Treatment Panel III criteria. Analyses were conducted separately for mothers and fathers. Logistic regression was used to estimate the associations.ResultsAfter adjusting for age, education, smoking, alcohol consumption and physical activity level of offspring, no significant association was found between father’s and their offspring’s MetS. Mother’s MetS was significantly and positively associated with their daughter’s MetS (adjusted odds ratio or adj OR: 1.63; 95% confidence Interval, CI:1.02-2.61), but not with their sons’ MetS. When analyzed by individual components, maternal impaired glucose (adj OR: 2.03; 95% CI: 1.02- 9.31), abdominal obesity (adj OR: 1.56; 95% CI: 0.98- 2.55) and low HDL-C (adj OR: 2.12; 95% CI: 1.36-3.32) were associated daughter’s MetS. Maternal low HDL-C and raised total cholesterol showed marginal association with son’s MetS. For fathers, only impaired glucose (adj OR: 4.91; 95% CI: 2.07- 11.68) was associated with their daughter’s MetS.ConclusionsUsing the data from Framingham Heart Study, we demonstrate differential association of MetS and its components between parents and offspring. Mother’s MetS was strongly related with daughter’s MetS, but the association was inconsistent with son’s MetS. No association was found between father’s MetS and offspring’s Mets. These results provide evidence that daughters with mother’s MetS are in higher risk than daughters or sons with father’s MetS.

Perceived neighborhood problems are associated with shorter telomere length in African American women

OBJECTIVES African Americans (AA) experience higher levels of stress related to living in racially segregated and poor neighborhoods. However, little is known about the associations between perceived neighborhood environments and cellular aging among adult AA. This study examined whether perceived neighborhood environments were associated with telomere length (TL) in AA after adjustment for individual-level risk factors. METHODS The analysis included 158 women and 75 men AA 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. Multivariable linear regression models were used to examine the associations of perceived neighborhood social cohesion, problems, and overall unfavorable perceptions with log-TL. RESULTS Women had significantly longer TL than men (0.59 vs. 0.54, p=0.012). After controlling for sociodemographic, and biomedical and psychosocial factors, a 1-SD increase in perceived neighborhood problems was associated with 7.3% shorter TL in women (Mean Difference [MD]=-0.073 (Standard Error=0.03), p=0.012). Overall unfavorable perception of neighborhood was also associated with 5.9% shorter TL among women (MD=-0.059(0.03), p=0.023). Better perceived social cohesion were associated with 2.4% longer TL, but did not reach statistical significance (MD=0.024(0.02), p=0.218). No association was observed between perceived neighborhood environments and TL in men. CONCLUSIONS Our findings suggest that perceived neighborhood environments may be predictive of cellular aging in AA women even after accounting for individual-level risk factors. Additional research with a larger sample is needed to determine whether perceived neighborhood environments are causally related to TL.

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.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 black population. Approach and Results— Participants were drawn from the Jackson Heart Study. Participant’s proportion 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 blacks.

Genetic Ancestry Is Associated With Measures of Subclinical Atherosclerosis in African Americans

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.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 black population. Approach and Results— Participants were drawn from the Jackson Heart Study. Participant’s proportion 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 blacks.

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

BackgroundCircadian 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 PLINKResultsWe 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.ConclusionsIn 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.