Date of Award

2012

Document type

Thesis

Degree Name

MSc by research (Master of Science by research)

First Supervisor

Dr Kevin Culligan

Second Supervisor

Dr Maria Morgan

Third Supervisor

Dr Paul O'Farrell & Dr Orna Tighe

Keywords

Diabetes Mellitus, Type 2, Insulin Resistance, Obesity, Adiponectin, Resistin .

Abstract

Low concentrations of adiponectin, the protein product of the adiponectin gene (ADIPOQ), and high concentrations of resistin have been reported to be associated with obesity and insulin resistance. Several adiponectin gene polymorphisms have been described, and their association with obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome, in different populations and sample types, is controversial. The purpose of the present study was to investigate the association of the two most well-known single nucleotide polymorphisms (SNPs) of ADIPOQ (+45T>G and +276G>T) with serum adiponectin concentrations, metabolic parameters associated with diabetes, and risk of T2DM in the Bahraini population. We also aimed to investigate the associations between serum adiponectin and resistin levels with the metabolic parameters and the prevalence of T2DM in Bahraini population.

We performed a cross-sectional study using a representative sample of 140 unrelated Bahraini patients with T2DM and 66 non-diabetic healthy subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the distribution of allele and genotype frequency of the SNP +45T>G polymorphism (exon2) and SNP +276G>T polymorphism (intron 2) in ADIPOQ. Lipid profile was measured by enzymatic methods. An ELISA was used to determine serum adiponectin and resistin levels.

It was observed that obesity, insulin resistance and T2DM are associated with low serum adiponectin levels. Compared with the control group, the T2DM group exhibited lower adiponectin levels and higher resistin levels. The G allele and TG/GG genotype of SNP +45T>G occurred more frequently than the common T allele and TT genotype in T2DM patients compared to the controls (PSNP +45T>G were associated with lower serum adiponectin levels. There was no statistically significant difference in allele and genotype frequencies of SNP +276G>T comparing control group with T2DM group.

No association with metabolic parameters was detected with either of the SNPs. In summary, our results demonstrated that, adiponectin SNP +45T>G, rather than SNP +276G>T is more associated with adiponectin levels. However, we could not confirm an association of these two SNPs with metabolic parameters of the metabolic syndrome.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.

File Size

2,940 KB

Comments

A thesis submitted to the Royal College of Surgeons for the degree of Master of Science, 2012.

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