An investigation into the underlying genetic determinates in obesity using the candidate-gene association approach and microarray technology

Martin, Glynn R. (2005) An investigation into the underlying genetic determinates in obesity using the candidate-gene association approach and microarray technology. Masters thesis, Memorial University of Newfoundland.

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Abstract

Introduction: (1) Ghrelin is a peptide and has been suggested involved in energy metabolism. (2) Physical activity plays an important role in the regulation of body fat. Generally, the body composition of obese people tend to be resistant to negative energy balance. Little is known, however, with respect to the molecular mechanism and basis underlying the differences of responsiveness between obese and non-obese humans. Methods: This study consists of two parts: ( 1) Genetic association of 3 single nucleotide polymorphisms (SNPs) in the ghrelin precursor gene (GHRL) with obesity phenotypes in the NL population ( 1182 subjects); (2) A global gene expression study of abdominal subcutaneous adipose tissue (ASAT) and comparison between lean and obese young men (10 subjects) in response to a 7-day aerobic exercise protocol using whole genome mRNA microarrays. Results: No significant association of any of the variant sites and body compositions or serum lipids was found in allele, genotype and haplotype analyses. In microarray experiment, the discoveries include, and to our knowledge the first time reported the differential regulations: 1) 6 inflammatory-related genes (SMPD3, CERK, ASAH2, ST3GAL5, ILJRIJ, and AGTRJ) within obese ASAT; 2) the genes in the lipolytic pathway (PRKACA, SLC27A6, ADCY6, ADCYAPJ, PPPJCB, DGAT2, and VLDLR); 3) the genes in the protein tyrosine phosphatase (PTP) pathway (PTPNJJ, PTPRD, and PTPN3) related to insulin sensitivity; 4) PPARA and PPRCJ that may favourably control energy metabolism in lean individuals, while not in obese. Conclusion: ( 1) The SNPs investigated within GHRL were not significantly associated with the variations of body composition and lipids in the NL population; (2) The genome-wide mRNA microarray expression study revealed many major differences of ASA T between obese and nonobese at the molecular level, with respect to the regulation of inflammation, lipolysis and insulin sensitivity.

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