An investigation of genetic polymorphism in association with Type 2 diabetes and metabolic syndrome.
Rachel M. Knott
Type 2 diabetes and metabolic syndrome are the metabolic disorders which constitute a major public health problem in both developed and developing countries. Various studies have suggested the genetic susceptibility to the disorders. The main aim of the thesis was to investigate the putative association of single nucleotide polymorphisms with Type 2 diabetes (T2D), metabolic syndrome (MetS) and the major components of metabolic syndrome. This study used metaanalysis, polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) and Sanger sequencing methods to analyse the results. The single nucleotide polymorphism rs57829442 of peroxisome proliferatoractivated receptorÎ³ coactivator1 (PPARGC1A) gene and its relation to risk of type 2 diabetes has been studied in the United Kingdom population. A metaanalysis of genetic variant rs8192678 (Gly482Ser) of peroxisome proliferatoractivated receptorÎ³ coactivator1 (PPARGC1A) gene and its association with the components of metabolic syndrome has been studied. An association of the genetic variants rs8192678 (Gly482Ser) of the PPARGC1A gene, rs7903146 of Transcription Factor 7 Like 2 (TCF7L2) gene, rs9939609 of Fat mass and obesityassociated (FTO) gene and rs1801282 (Pro12Ala) of peroxisome proliferatoractivated receptor gamma (PPARG) gene with the metabolic syndrome and its components has been studied in the Nepalese population. The results showed that variant rs57829442 of PPARGC1A is not associated with T2D in the United Kingdom population. Further investigation with increased sample size is warranted. In the metaanalysis, the variant rs8192678 (Gly482Ser) of PPARGC1A gene was found to be significantly associated with body mass index (BMI) in Asian populations under dominant genetic model, total cholesterol (TC) in nonAsian population under recessive genetic model and with fasting plasma glucose (FPG) under a recessive model in overall and nonAsian populations. No significant association of the variants rs8192678 (Gly482Ser), rs7903146, rs9939609 and rs1801282 (Pro12 Ala) was found associated with MetS under dominant, recessive, codominant and additive models in the Nepalese population. However, the genotypes (AG and AA) of rs8192678 (Gly482Ser) had a statistically significant protective effect on systolic blood pressure. The genotypes with the risk allele of rs9930609 of FTO gene was significantly associated with weight, waist circumference and diastolic blood pressure under dominant genetic model and with BMI under both dominant and recessive genetic models in the Nepalese population. To the best of our knowledge, this is the first study to report the findings in the Nepalese population.
|Publication Date||May 1, 2018|
|Institution Citation||BHATTA, P. 2018. An investigation of genetic polymorphism in association with Type 2 diabetes and metabolic syndrome. Robert Gordon University, PhD thesis.|
|Keywords||Type 2 diabetes; Metabolic syndrome; Single nucleotide polymorphism; PPARGC1APPARGTCF7L2FTO|
BHATTA 2018 An investigation of genetic
Copyright: the author and Robert Gordon University
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