LIST OF TABLES Table 2.1: Fasting Plasma Glucose Test Table 2.2: Oral Glucose Tolerance Table 2.3: T2D susceptibility genes Table 2.4: Compiled inforamation about Human Sirtuins (SIRT1-SIRT7) Table 3.1: Composition of contents used for PCR master mix preparation Table 3.2: Candidate gene polymorphisms and their PCR conditions Table 3.3: Composition of contents used for restriction digestion master mix preparation Table 4.1: Comparison of clinical characteristics among cases and healthy controls in Banias Table 4.2: Comparison of clinical characteristics among cases and healthy controls in BCs Table 4.3: Comparison of clinical characteristics among cases and healthy controls in Brahmins Table 4.4: Comparison of clinical characteristics among cases and healthy controls in Jat Sikhs Table 4.5: Comparison of clinical characteristics among cases and healthy controls in Khatris Table 4.6: Comparison of clinical characteristics among cases and healthy controls in Rajputs Table 4.7: Comparison of clinical characteristics among cases and healthy controls in SCs Table 4.8: Comparison of clinical characteristics among cases and healthy controls in pooled population of Punjab Table 4.9 (a): Comparison of clinical characteristics within genotypes of PGC-1α (Gly482Ser) polymorphism in Banias, BCs and Brahmins of Punjab Table 4.9 (b): Comparison of clinical characteristics within genotypes of PGC-1α (Gly482Ser) polymorphism in Jat Sikhs, Khatris, Rajputs, SCs and pooled population of Punjab Table 4.10 (a): Comparison of clinical characteristics within genotypes of UCP2 -866 G>A polymorphism in Banias, BCs, Brahmins and Jat Sikhs of Punjab Table 4.10 (b): Comparison of clinical characteristics within genotypes of UCP2 -866 G>A polymorphism in Khatris, Rajputs, SCs and pooled population of Punjab Table 4.11 (a): Comparison of clinical characteristics within genotypes of SIRT1 -1400 T>C polymorphism in Banias, BCs, Brahmins and Jat Sikhs of Punjab Table 4.11 (b): Comparison of clinical characteristics within genotypes of SIRT1 -1400 T>C polymorphism in Khatris, Rajputs, SCs and pooled population of Punjab Table 4.12: Caste wise association of epidemiology and molecular analysis Table 5.1: P values and Odds ratios of the studies showing positive association of PGC1α (Gly482Ser) polymorphism with T2D Table 5.2: P values and Odds ratios of the studies showing positive association of UCP2 -866 G>A polymorphism with T2D List of figures Figure 2.1: Disorders of glycemia etiological type and stages. Figure 2.2: Comparison of Indian & World diabetic population. Source Figure 2.3: Pictorial representation and examples of the ‘Thrifty genotype’ hypothesis. Figure 2.4: The various factors that contribute to the pathogenesis of T2D affecting both insulin secretion and insulin action pathways. Figure 2.5: Organisation of the human PGC-1α gene. Figure 2.6: Organisation of the human UCP2 gene. Exons are depicted as black boxes and non coding exons are depicted as grey boxes Figure 2.7: Proton leak pathways carried out in mitochondria mediated through UCPs and ANT. Figure 2.8: Mechanism by which UCP2 mediated mitochondrial dysfunction disrupts insulin secretion. Figure 2.9: Organisation of the Human SIRT1 gene. Figure 2.10: Tissue specific functions of SIRT1 in metabolism. Figure 3.1: The in-silico PCR amplified product of PGC 1α (Gly482Ser) polymorphism obtained from UCSC genome browser. Figure 3.2: The in-silico PCR amplified product of UCP2 -866 G>A polymorphism obtained from UCSC genome browser Figure 3.3: The in silico PCR amplified product of SIRT1 -1400 T>C polymorphism obtained from UCSC genome browser. Figure 3.4: Restriction site of enzyme (MspI) desired to digest the PGC 1α (Gly482Ser) polymorphism amplified PCR product showing one restriction site. Figure 3.5: Restriction site of enzyme (MluI) desired to digest the UCP2 -866 G>A polymorphism amplified PCR product showing one restriction site. Figure 4.1: Distribution of WHR, hypertension and WC pattern among cases and controls in Banias of Punjab. Figure 4.2:. Distribution of WHR, hypertension and WC among cases and controls in BCs of Punjab. Figure 4.3:. Distribution of WHR, hypertension and WC among cases and controls in Brahmins of Punjab. Figure 4.4:. Distribution of WHR, hypertension and WC among cases and controls in Jat Sikhs of Punjab. Figure 4.5:. Distribution of WHR, hypertension and WC among cases and controls in Khatris of Punjab. Figure 4.6: Distribution of WHR, hypertension and WC among cases and controls in Rajputs of Punjab. Figure 4.7: Distribution of WHR, hypertension and WC among cases and controls in SCs of Punjab. Figure 4.8: Distribution of WHR, hypertension and WC among cases and controls in pooled population of Punjab. Figure 4.9: Distribution of WHR, hypertension and WC among Males in pooled population of Punjab. Figure 4.10: Distribution of WHR, hypertension and WC among females in pooled population of Punjab. Figure 4.11: DNA quality-check at 0.8% agarose. 3μl of diluted DNA samples were loaded in each well. Figure 4.12: Restriction digestion profiles of PCR amplified PGC-1α DNA fragment digested with Msp I enzyme showing heterozygote (H) and mutant type (M) genotypes. Figure 4.13: The allele and genotypic frequency distribution of PGC-1α (Gly482Ser) polymorphism in Banias of Punjab. Figure 4.14: The allele and genotypic frequency distribution of PGC-1α (Gly482Ser) polymorphism in BCs of Punjab. Figure 4.15: The allele and genotypic frequency distribution of PGC-1α (Gly482Ser) polymorphism in Brahmins of Punjab. Figure 4.16: The allele and genotypic frequency distribution of PGC-1α (Gly482Ser) polymorphism in Jat Sikhs of Punjab. Figure 4.17: The allele and genotypic frequency distribution of PGC-1α (Gly482Ser) polymorphism in Khatris of Punjab. Figure 4.18: The allele and genotypic frequency distribution of PGC-1α (Gly482Ser) polymorphism in Rajputs of Punjab. Figure 4.19: The allele and genotypic frequency distribution of PGC-1α (Gly482Ser) polymorphism in SCs of Punjab. Figure 4.20: The allele and genotypic frequency distribution of PGC-1α (Gly482Ser) polymorphism in pooled population of Punjab. Figure 4.21: The allele and genotype frequency distribution of the PGC-1α (Gly482Ser) polymorphism in males of Punjab. Figure 4.22: The allele and genotype frequency distribution of the PGC-1α (Gly482Ser) polymorphism in females of Punjab. Figure 4.23: Restriction digestion profiles of PCR amplified UCP2 DNA fragment digested with Mlu I enzyme showing wild type (W), heterozygote (H) and mutant type (M) genotypes. Figure 4.24: The allele and genotypic frequency distribution of UCP2 -866 G>A polymorphism among cases and controls in Banias of Punjab. Figure 4.25: The allele and genotypic frequency distribution of UCP2 -866 G>A polymorphism among cases and controls in BCs of Punjab. Figure 4.26: The allele and genotypic frequency distribution of UCP2 -866 G>A polymorphism among cases and controls in Brahmins of Punjab. Figure 4.27: The allele and genotypic frequency distribution of UCP2 -866 G>A polymorphism among cases and controls in Jat Sikhs of Punjab. Figure 4.28: The allele and genotypic frequency distribution of UCP2 -866 G>A polymorphism among cases and controls in Khtaris of Punjab. Figure 4.29: The allele and genotypic frequency distribution of UCP2 -866 G>A polymorphism among cases and controls in Rajputs of Punjab. Figure 4.30: The allele and genotypic frequency distribution of UCP2 -866 G>A polymorphism among cases and controls in SCs of Punjab. Figure 4.31: The allele and genotypic frequency distribution of UCP2 -866 G>A polymorphism in pooled population of Punjab. Figure 4.32: The allele and genotypic frequency distribution of UCP2 -866 G>A polymorphism in males of Punjab. Figure 4.33: The allele and genotypic frequency distribution of UCP2 -866 G>A polymorphism in females of Punjab. Figure 4.34: Partial electropherogram of amplified SIRT1 promoter showing TT wild type genotype of SIRT1 -1400T>C polymorphism Figure 4.35: Partial electropherogram of amplified SIRT1 promoter showing TC heterozygote genotype of SIRT1 -1400T>C polymorphism Figure 4.36: Partial electropherogram of amplified SIRT1 promoter showing CC mutant type genotype of SIRT1 -1400T>C polymorphism Figure 4.37: The allele and genotypic frequency distribution of SIRT1 -1400 T>C polymorphism among cases and controls in Banias of Punjab. Figure 4.38: The allele and genotypic frequency distribution of SIRT1 -1400 T>C polymorphism among cases and controls in BCs of Punjab. Figure 4.39: The allele and genotypic frequency distribution of SIRT1 -1400 T>C polymorphism among cases and controls in Brahmins of Punjab. Figure 4.40: The allele and genotypic frequency distribution of SIRT1 -1400 T>C polymorphism among cases and controls in Jat Sikhs of Punjab. Figure 4.41: The allele and genotypic frequency distribution of SIRT1 -1400 T>C polymorphism among cases and controls in Khatris of Punjab. Figure 4.42: The allele and genotypic frequency distribution of SIRT1 -1400 T>C polymorphism among cases and controls in Rajputs of Punjab. Figure 4.43: The allele and genotypic frequency distribution of SIRT1 -1400 T>C polymorphism among cases and controls in SCs of Punjab. Figure 4.44: The allele and genotypic frequency distribution of SIRT1 -1400 T>C polymorphism among cases and controls in pooled population of Punjab. Figure 4.45: The allele and genotypic frequency distribution of SIRT1 -1400 T>C polymorphism among cases and controls in males of Punjab. Figure 4.46: The allele and genotypic frequency distribution of SIRT1 -1400 T>C polymorphism among cases and controls in females of Punjab.
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