Bibiana Garcia-Bailo

Population Admixture Associated With Disease Prevalence in the Boston Puerto Rican Health Study

Older Puerto Ricans living in the continental U.S. suffer from higher rates of diabetes, obesity, cardiovascular disease and depression compared to non-Hispanic White populations. Complex diseases, such as these, are likely due to multiple, potentially interacting, genetic, environmental and social risk factors. Presumably, many of these environmental and genetic risk factors are contextual. We reasoned that racial background may modify some of these risk factors and be associated with health disparities among Puerto Ricans. The contemporary Puerto Rican population is genetically heterogeneous and originated from three ancestral populations: European settlers, native Taíno Indians, and West Africans. This rich-mixed ancestry of Puerto Ricans provides the intrinsic variability needed to untangle complex gene–environment interactions in disease susceptibility and severity. Herein, we determined whether a specific ancestral background was associated with either of four major disease outcomes (diabetes, obesity, cardiovascular disease, and depression). We estimated the genetic ancestry of 1,129 subjects from the Boston Puerto Rican Health Study based on genotypes of 100 ancestry informative markers (AIMs). We examined the effects of ancestry on tests of association between single AIMs and disease traits. The ancestral composition of this population was 57.2% European, 27.4% African, and 15.4% Native American. African ancestry was negatively associated with type 2 diabetes and cardiovascular disease, and positively correlated with hypertension. It is likely that the high prevalence rate of diabetes in Africans, Hispanics, and Native Americans is not due to genetic variation alone, but to the combined effects of genetic variation interacting with environmental and social factors.

Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: modulation of inflammation and oxidative stress.

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide, and certain population subgroups are especially vulnerable to the disease. To reduce T2DM risk and progression at the population level, preventative strategies are needed that can be implemented on a population-wide scale with minimal cost and effort. Chronic low-grade inflammation resulting from oxidative stress and imbalances in the innate immune system has been associated with obesity, metabolic syndrome, and insulin resistance – critical stages in the development and progression of T2DM. Therefore, inflammation may play a causal role in the pathogenesis of T2DM, and reducing it via modulation of oxidative stress and the innate immune response could lead to a status of improved insulin sensitivity and delayed disease onset. Dietary supplementation with anti-inflammatory and antioxidant nutritional factors, such as micronutrients, might present a novel strategy toward the prevention and control of T2DM at the population level. This review examines current knowledge linking oxidation, inflammatory signaling pathways, and vitamin supplementation or intake to the risk of T2DM. The concept that micronutrients, via attenuation of inflammation, could be employed as a novel preventive measure for T2DM is evaluated in the context of its relevance to public health.

PPARGC1A variation associated with DNA damage, diabetes, and cardiovascular diseases: the Boston Puerto Rican Health Study.

OBJECTIVE—Individuals with type 2 diabetes exhibit higher DNA damage and increased risk of cardiovascular disease (CVD). However, mechanisms underlying the association between DNA damage and development of type 2 diabetes and CVD are not understood. We sought to link peroxisome proliferator–activated receptor-γ coactivator-1 α (PPARGC1A), a master transcriptional regulator of mitochondrial oxidative phosphorylation and cellular energy metabolism, with DNA damage, type 2 diabetes, and CVD. RESEARCH DESIGN AND METHODS—We measured DNA damage as urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration and examined the relationship between nine PPARGC1A genetic variants, DNA damage, type 2 diabetes, and self-reported CVD in 959 participants of the Boston Puerto Rican Health Study. RESULTS—With respect to urinary 8-OHdG, PPARGC1A variants showed significant association, and PPARGC1A haplotypes exhibited significant association after correction for multiple testing. Two independent PPARGC1A variants associated significantly with type 2 diabetes (odds ratios [ORs] 1.35 and 2.46; P = 0.045 and <0.001). Carriers of minor alleles of two other PPARGC1A variants, both in strong linkage disequilibrium and associated with lower DNA damage, showed lower prevalence of CVD (ORs 0.53 and 0.65; P = 0.030 and 0.175). Moreover, we found that physical activity correlated negatively with DNA damage. CONCLUSIONS—It is plausible that low physical activity combined with risk haplotyes contribute to the high prevalence of type 2 diabetes in this population. We propose that PPARGC1A influences development of type 2 diabetes and CVD via DNA damage. Increasing physical activity, which induces PPARGC1A expression, is a potential strategy to slow DNA damage, thereby decreasing the risk of CVD for individuals with type 2 diabetes.

Dietary patterns and ethnicity are associated with distinct plasma proteomic groups

BACKGROUND High-abundance plasma proteins are involved in disease-associated pathways and are useful in the diagnosis of nutritional and disease states. However, little is known about how concentrations of many plasma proteins vary between individuals from different ethnocultural groups with different dietary habits. OBJECTIVE We explored the association between plasma proteomic groups, dietary patterns, and ethnicity in the Toronto Nutrigenomics and Health Study, an ethnically diverse population of healthy young adults. DESIGN Concentrations of 54 high-abundance plasma proteins were measured simultaneously by liquid chromatography/multiple-reaction monitoring-mass spectrometry in 1090 individuals. Principal components analysis was used to identify plasma proteomic groups. Linear regression was used to investigate relations between proteomic groups and previously identified dietary patterns (Western, prudent, Eastern). Differences in individual protein concentrations between ethnocultural groups were tested by using general linear models. RESULTS Four independent principal components representative of proteomic groups were identified. Principal components 1 and 2 included proteins from multiple pathways. Component 3 was inflammatory, and component 4 included coagulation cascade proteins. East Asians and South Asians had lower component 1 scores, and East Asians had higher component 2 scores. South Asians had higher average scores for component 3. Individual protein concentrations also varied across ethnocultural groups. Principal component 1 was positively associated with the Western dietary pattern and inversely associated with the Eastern pattern. Component 3 was positively associated with the Eastern pattern. CONCLUSIONS Plasma proteomic groups differ between young adults of diverse ethnocultural groups with different dietary habits. These differences may partly account for different rates of cardiometabolic disease later in life.

Disparities in allele frequencies and population differentiation for 101 disease-associated single nucleotide polymorphisms between Puerto Ricans and Non-Hispanic Whites

BackgroundVariations in gene allele frequencies can contribute to differences in the prevalence of some common complex diseases among populations. Natural selection modulates the balance in allele frequencies across populations. Population differentiation (FST) can evidence environmental selection pressures. Such genetic information is limited in Puerto Ricans, the second largest Hispanic ethnic group in the US, and a group with high prevalence of chronic disease. We determined allele frequencies and population differentiation for 101 single nucleotide polymorphisms (SNPs) in 30 genes involved in major metabolic and disease-relevant pathways in Puerto Ricans (n = 969, ages 45–75 years) and compared them to similarly aged non-Hispanic whites (NHW) (n = 597).ResultsMinor allele frequency (MAF) distributions for 45.5% of the SNPs assessed in Puerto Ricans were significantly different from those of NHW. Puerto Ricans carried risk alleles in higher frequency and protective alleles in lower frequency than NHW. Patterns of population differentiation showed that Puerto Ricans had SNPs with exceptional FST values in intronic, non-synonymous and promoter regions. NHW had exceptional FST values in intronic and promoter region SNPs only.ConclusionThese observations may serve to explain and broaden studies on the impact of gene polymorphisms on chronic diseases affecting Puerto Ricans.

The association between obesity, cardiometabolic disease biomarkers, and innate immunity-related inflammation in Canadian adults

Introduction Obesity is associated with a state of chronic inflammation, and increased cardiometabolic disease risk. The present study examined the relationship between body mass index (BMI) and cardiometabolic and inflammatory biomarkers among normal weight, overweight, and obese Canadian adults. Methods Subjects (n = 1805, aged 18 to 79 years) from the Canadian Health Measures Survey (CHMS) were examined for associations between BMI, cardiometabolic markers (apolipoprotein [Apo] A1, ApoB, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol, total cholesterol/HDL ratio [total:HDL-C ratio], triglycerides, and glycosylated hemoglobin [HbA1c]), inflammatory factors (C-reactive protein [CRP], fibrinogen, and homocysteine), and 25-hydroxyvitamin D [25(OH)D]. Bootstrap weights for variance and sampling weights for point estimates were applied to account for the complex survey design. Linear regression models adjusted for age, sex, physical activity, smoking status, and ethnicity (in addition to season of clinic visit, for vitamin D analyses only) were used to examine the association between cardiometabolic markers, inflammatory factors, and BMI in Canadian adults. Results All biomarkers were significantly associated with BMI (P ≤ 0.001). ApoA1 (β = −0.31, P < 0.0001), HDL-C (β = −0.61, P < 0.0001), and 25(OH)D (β = −0.25, P < 0.0001) were inversely associated with BMI, while all other biomarkers showed positive linear associations. Distinct patterns of association were noted among normal weight, overweight, and obese groups, excluding CRP which showed a significant positive association with BMI in the overall population (β = 2.80, P < 0.0001) and in the normal weight (β = 3.20, P = 0.02), overweight (β = 3.53, P = 0.002), and obese (β = 2.22, P = 0.0002) groups. Conclusions There is an apparent profile of cardiometabolic and inflammatory biomarkers that emerges as BMI increases from normal weight to obesity. Understanding these profiles may permit developing an effective approach for early risk prediction for cardiometabolic disease.

Plasma Vitamin D and Biomarkers of Cardiometabolic Disease Risk in Adult Canadians, 2007–2009

Introduction Vitamin D may modulate cardiometabolic disease risk, although the relationship has not been investigated in the general Canadian population. Understanding this relationship may inform public health strategies to curb the incidence of cardiometabolic disease in Canada and elsewhere. The objectives of this study were to examine the association between vitamin D and traditional and novel biomarkers of cardiometabolic disease and to describe the extent of the month-to-month fluctuations of vitamin D in the Canadian population. Methods We examined the association between plasma 25-hydroxyvitamin D and a range of cardiometabolic risk biomarkers in participants (n = 1,928; age range, 16–79 years) from the Canadian Health Measures Survey. We conducted linear regressions analyses (adjusted for sex, waist circumference, physical activity, hormone use, and season) to assess the relationship between 25-hydroxyvitamin D and biomarkers of dysglycemia, dyslipidemia, and inflammation in the study population. We repeated analyses stratified by sex, and we evaluated monthly fluctuations in 25-hydroxyvitamin D in men and women. Results We observed wide month-to-month variations in 25-hydroxyvitamin D; fluctuations were more pronounced in men. Plasma 25-hydroxyvitamin D was inversely associated with insulin, insulin resistance, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and the ratio of total to high-density lipoprotein cholesterol but not with fasting glucose, apolipoprotein A1, apolipoprotein B, C-reactive protein, fibrinogen, or homocysteine. This pattern varied between men and women. Conclusion Vitamin D may modulate various metabolic processes and may influence cardiometabolic disease risk in Canadians. These findings may have public health implications when recommending vitamin D for the prevention of cardiometabolic disease and related conditions.

WDTC1, the Ortholog of Drosophila Adipose Gene, Associates With Human Obesity, Modulated by MUFA Intake

Adipose (adp) is an obesity gene in Drosophila and mice with crucial functions in fat metabolism. We investigated the correlation between genetic variation of the WDTC1 locus, the ortholog of adp, and human obesity. Five WDTC1 single‐nucleotide polymorphisms (SNPs) were genotyped in 935 and 1,115 adults of two ethnically diverse US populations. In the Boston Puerto Rican population, we demonstrated that two WDTC1 SNPs strongly associated with obesity. Homozygote and heterozygote carriers of the major allele i22835A, representing ∼96% of the population, had significantly higher mean BMI (31.5 and 31.0 kg/m2, respectively) than noncarriers (28.6 kg/m2). Conversely, homozygotes of the minor allele i22835G were leaner and were 74% less likely to be overweight or obese (odds ratio (OR) = 0.26, P = 0.003) compared to homozygote carriers of the major allele. Haplotype analyses based on two SNPs further supported these findings. In addition, we found a strong interaction of monounsaturated fatty acid (MUFA) intake by genotype in this population. As dietary MUFA intake increased, minor allele carriers of SNP i22835A>G had higher BMIs, whereas major allele carriers had lower BMIs. A white population also exhibited a pattern of association between WDTC1 genotypes and obesity although of a different nature. Those WDTC1 variants which associated with obesity likely have experienced strong positive selection in human history, when food supply was unpredictable. Given the high frequency of the major alleles in both populations, we suggest that WDTC1 variation may be an important risk factor contributing to obesity in these populations.

Genetic Determinants of Dietary Antioxidant Status

Oxidative stress refers to a physiological state in which an imbalance between pro-oxidants and antioxidants results in oxidative damage. Oxidative stress has been associated with the development of numerous chronic diseases such as type 2 diabetes, cardiovascular disease (CVD), osteoporosis, and cancer. Endogenous production of free radicals occurs during normal physiological processes, such as aerobic metabolism, oxidation of biological molecules, and enzymatic activity. Environmental factors such as ultraviolet radiation, air pollution, and cigarette smoking can also contribute to the accumulation of free radicals in the body. Excess free radicals can damage tissues and promote the upregulation of disease-related pathways such as inflammation. Modulating oxidative stress by dietary supplementation with antioxidant micronutrients such as vitamins C and E or phytochemicals such as different carotenoids may help prevent or delay the development of certain diseases. However, research on antioxidant supplementation and disease has yielded inconsistent findings, which may be due, in part, to interindividual genetic variation. Polymorphisms in genes coding for endogenous antioxidant enzymes or proteins responsible for the absorption, transport, distribution, or metabolism of dietary antioxidants have been shown to affect antioxidant status and response to supplementation. These genetic variants may also interact with environmental factors, such as diet, to determine an individuals overall antioxidant status. This chapter examines current knowledge of the relationship between genetic variation and dietary antioxidant status.

Novel Effects of Hormonal Contraceptive Use on the Plasma Proteome

Background Hormonal contraceptive (HC) use may increase cardiometabolic risk; however, the effect of HC on emerging cardiometabolic and other disease risk factors is not clear. Objectives To determine the association between HC use and plasma proteins involved in established and emerging disease risk pathways. Method Concentrations of 54 high-abundance plasma proteins were measured simultaneously by LC-MRM/MS in 783 women from the Toronto Nutrigenomics and Health Study. C-reactive protein (CRP) was measured separately. ANCOVA was used to test differences in protein concentrations between users and non-users, and among HC users depending on total hormone dose. Linear regression was used to test the association between duration (years) of HC use and plasma protein concentrations. Principal components analysis (PCA) was used to identify plasma proteomic profiles in users and non-users. Results After Bonferroni correction, 19 proteins involved in inflammation, innate immunity, coagulation and blood pressure regulation were significantly different between users and non-users (P<0.0009). These differences were replicated across three distinct ethnocultural groups. Traditional markers of glucose and lipid metabolism were also significantly higher among HC users. Neither hormone dose nor duration of use affected protein concentrations. PCA identified 4 distinct proteomic profiles in users and 3 in non-users. Conclusion HC use was associated with different concentrations of plasma proteins along various disease-related pathways, and these differences were present across different ethnicities. Aside from the known effect of HC on traditional biomarkers of cardiometabolic risk, HC use also affects numerous proteins that may be biomarkers of dysregulation in inflammation, coagulation and blood pressure.