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Title: Studies on Telomere Length and Telomerase Activity in Obesity Associated States with Special Reference to Type 2 Diabetes
Authors: Rasha Mazen Mohammad Alkaldiy 
Supervisor: د. اليوشيجن موجيميني
Keywords: Tellomere Lengtth Tellomerase Acttiiviitty Obesiitty
Issue Date: 2015
Publisher:  Kuwait university - college of graduate studies
Abstract: The main hypothesis of this research is that Type 2 diabetes mellitus [T2DM] is associated with shorter telomeres and this relationship might be mediated by insulin resistance [IR] and modified by single nucleotide polymorphisms [SNPs] in telomerase and telomere related genes. We also hypothesize that a functional variant in the Uncoupling Binding Protein 2 [UCP2] gene involved in the mitochondrial production of reactive oxygen species will be associated with shorter telomere lengths in T2DM patients, in whom oxidative stress is elevated. The objectives of this research are to optimize local methods for measuring telomere length and to explore if there is an association between telomere length, telomerase levels, obesity related metabolic factors and T2DM. Indices of obesity (Body Mass Index [BMI], Waist Circumference [WC], Waist to height Ratio [WHtR], Body Fat [BF%]), Telomerase Reverse Transcriptase [hTERT], total adiponectin, high molecular weight adiponctin, insulin, myeloperoxidase [MPO], Total Oxidative stress status [TOS] and leukocyte Telomere Length [LTL] were measured in 225 T2DM patients and 245 age and sex matched controls. IR was estimated using Homeostasis Model Assessment [HOMA-IR] calculator. Allelic Discrimination (AD) was used to genotype SNPs in telomerase and telomere binding proteins genes. Results showed that T2DM patients had significantly shorter LTL and lower hTERT levels compared to controls. Higher BMI, WC and WHtR were associated with higher risk of shorter telomeres and lower levels of hTERT. Other obesity related factors such as HOMA-IR, hyper-insulinemia and oxidative stress markers were also associated with higher risk of short telomeres and lower levels of hTERT. Nevertheless, higher levels of adiponectin were associated with lower risk of shorter telomeres. T2DM was significantly associated with higher risk of shorter telomere lengths and lower levels of hTERT. [G/G] genotype of SNP rs12696304 was significantly associated with shorter telomeres, lower levels of hTERT, hypoadiponectinemia and higher anthropometric measures. [C/C] vii genotype of SNP rs16847897 showed similar trends. Metabolic changes such as the dys-regulation of adiponectin, hyper-insulinemia, IR, obesity associated inflammatory process are associated with short telomeres, lower levels of telomerase and hence, could play a role in mediating telomere shortening. Since, incidence of obesity and T2DM are increasing at epidemic pace in Kuwait; telomere attrition and telomerase levels could be potential cardio-metabolic risk markers of obesity and T2DM. Our findings could have broad relevance for both normal and pathological age associated processes.
Appears in Programs:0570 Pathology (Ph.D.)

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