Investigations into obesity using anthropometric, serum and genetic markers

Kennedy, Aaron P. (2010) Investigations into obesity using anthropometric, serum and genetic markers. Masters thesis, Memorial University of Newfoundland.

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Abstract

Obesity is one of today's most visible public health problems with worldwide incidence at over a billion people. To understand such a vast problem requires one to study the issue from different angles. This includes studying how obesity is measured, and how metabolic and genetic factors influence the obesity phenotype. This thesis investigates the accuracy of the body mass index, a trusted measurement tool, compared to an industry standard measuring tool DXA. It also investigates the effects of serum calcium on serum lipid levels and how polymorphisms in two genes associated with the storage of fat in the human adipocyte affect obesity phenotypes. -- Although body mass index (BMI) is the most widely used measure of obesity, debate still exists on how accurately BMI defines obesity. In this study, adiposity status defined by BMI and DXA were compared in a large population to evaluate the accuracy of BMI. A total of 1691 adult volunteers from Newfoundland and Labrador (NL) participated in the study. BMI and %BF were measured for all subjects following a 12 hour fasting period. Subjects were categorized as underweight (UW), normal weight (NW), overweight (OW), or obese (OB) based on BMI and %BF criteria. Differences between the two methods were compared within gender and by age groups. According to BMI criteria 1.2% of women were classified as UW, 44.4% as NW, 34.1% as OW and 20.3% as OB. When women were classified according to %BF criteria 2.2% were UW, 29.7% were NW, 31.0% were OW and 37.1% were OB. The overall discrepancy between the two methods for women was substantial at 34.8% (14.6 % for NW and 16.9% for OB, p<0.001). In men the overall discrepancy was 35.2% between BMI and DXA (17.6% for QW and 13.5% for OB, p<0.001). Misclassification by BMI was dependent on age, gender and adiposity status. In conclusion, BMI misclassified adiposity status in approximately one third of women and men compared with DXA. Caution should be taken when BMI is used in clinical and scientific research as well as clinical practice. -- Some epidemiological evidence shows a link between abnormality of lipid profiles and variations in serum calcium. However, it is unknown whether this result was influenced by confounding factors. The present study was designed to investigate the relationship between serum lipids and calcium. Serum calcium was corrected for albumin. Major confounding factors including age, gender, medications, menopause, parathyroid hormone (PTH) and 25-OH-vitamin D status were controlled in analyses. A total of 1907 adult subjects from the province of Newfoundland and Labrador (NL), Canada participated in the study. Significant positive correlations were detected between serum total cholesterol and high density lipoprotein-cholesterol (HDL-c) with variations of serum Ca⁺⁺ in both genders (p<0.05-0.0001). Significant positive correlations were additionally detected between triglycerides (TAG) and low density lipoprotein-cholesterol (LDL-c) with Ca⁺⁺ in women only (p<0.0001) in partial correlation analyses. Similar significant results were detected in both females and males not taking any medication. Analyses were performed based on menopausal status as well. Significant correlations were seen in both pre- and post-menopausal women but higher correlation coefficients were observed in pre-menopausal women as compared to post-menopausal women. Subjects with low calcium levels had the lowest concentration of total cholesterol, TAG, HDL-c and LDL-c, while subjects with high calcium levels had the highest concentration of all four markers in women. The significant associations between cholesterol, TAG and LDL-c and serum Ca⁺⁺ remained after calcium was adjusted for 25-OH-vitamin D and PTH. Our results indicate that the abnormality of serum lipid profiles are significantly correlated with altered serum Ca⁺⁺ levels independent of age, obesity status, medication, phosphorus, magnesium, 25-OH-vitamin D and PTH. -- Perilipin (PLIN) is the major component of lipid droplet coating proteins, which play a key role in regulating human adipocyte triglyceride metabolism. Adipophilin is another lipid droplet coating protein that has been implicated to be involved in subcellular lipid trafficking. The association of perilipin and adipophilin with lipid storage droplets and lipid trafficking makes them potential candidate genes for obesity and lipid abnormality. -- This study investigated whether single nucleotide polymorphisms (SNP) in the PLIN and ADFP genes are associated with variations in body composition and serum lipid abnormalities. A total of 1269 healthy subjects (1002 females, 267 males) were recruited from the genetically homogeneous population of Newfoundland and Labrador (NL), Canada. All subjects were at a minimum third generation residents of NL, between the ages of 19-62. Percentages body fat (%FAT) was measured using DXA. Fasting serum concentrations of glucose, cholesterol, triacylglyceride (TAG), HDL-C, LDL-C, and insulin were measured and the risk ratio for cardiovascular disease (cholesterol/HDL-C) was calculated. Genomic DNA was extracted from whole blood. All statistical analyses were performed using the statistical software R or SPSS software version 16 for Windows; with significance set at p<0.05. Hardy-Weinberg equilibrium was tested using chi-square analysis. -- Three SNPs located within the PLIN coding region were selected. SNP:rs4932241, an A/C SNP located in the 3' untranslated region, SNP:rs2289487, an A/G SNP located between the 2nd and 3rd exon, and SNP:rs894160, an A/G SNP located between the 6th and 7th exon. In ADFP, two A/G polymorphisms were selected. SNP:rs3824369 located in the 5' intronic region and SNP:rs35629534 located in the 3' untranslated region. Genotyping was performed using TaqMan® validated SNP genotyping assays from Applied Biosystems on an ABI 7000 Sequence Detection System. All SNPs investigated in this study were in Hardy Weinberg equilibrium. -- The results showed that there were no significant associations within the PLIN SNPs for body composition or serum lipid parameters in our population. The results of the present study do not support a significant role for genetic variations within the perilipin gene in the regulation of body composition and serum lipid profiles in the NL population. -- The results revealed a significant association between ADFP SNP:rs3824369 and %BF, serum cholesterol and serum LDL-c after controlling for the effects of gender and age. Carriers of the major allele of SNP:rs3824369 had significantly higher fasting levels of LDL-c and significantly higher fasting levels of serum cholesterol compared to homozygote carriers of the minor allele. In addition, carriers of the major allele of SNP:rs3824369 had significantly higher %BF compared to homozygote carriers of the minor allele. To our knowledge this is the first report of an association between a SNP in ADFP and variations in body fat or serum lipids.

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