ABSTRACT
Proper vascular function is important for well-being of mother and growing fetus. VEGFTOTAL, and VEGF165b levels and its vascular endothelial complications in gestational diabetes mellitus (GDM) together with the association of inflammation and advanced glycation end products (AGEs) are less studied. VEGF165b/VEGFTOTAL (VEGF RATIO) in GDM pregnant women was investigated in this study. Plasma VEGFTOTAL was lower in GDM (17.68 ± 1.30 pg/mL) compared to non-GDM (25.69 ± 1.40 pg/mL). VEGF165b, ICAM-1, and AGEs were higher in GDM (9.9 ± 1.4 pg/mL, 201.04 ± 7.85 µg/mL, and 10.40 ± 0.98 µg/mL, respectively) and lower in non-GDM (6.47 ± 0.70 pg/mL, 174.1 ± 7.11 µg/mL, and 4.71 ± 0.39 µg/mL, respectively). Compared to non GDM (0.25 ± 0.02), VEGF RATIO was higher in GDM (0.45 ± 0.04) and correlated with -ICAM-1 (r = 0.375, p < .001) and AGEs (r = 0.199, p < .05). Tertile stratification of VEGF RATIO implied that frequency of GDM increases with increasing tertiles of VEGF RATIO (p for trend <.001). Association of VEGF RATIO with GDM was significant even after adjusting for AGEs (OR = 1.279, CI = 1.118-1.462, p < .0010) but it lost its significance when adjusted for ICAM-1 (OR = 1.006, CI = 0.995-1.017, p = .308). VEGF RATIO plays an important role in GDM in association with vascular inflammation.
Subject(s)
Diabetes, Gestational/blood , Vascular Endothelial Growth Factor A/blood , Adult , Blood Glucose/analysis , Blood Glucose/metabolism , Case-Control Studies , Female , Glycation End Products, Advanced/blood , Humans , Intercellular Adhesion Molecule-1/blood , Peptide Fragments/blood , Pregnancy , Pregnancy Complications, Cardiovascular/blood , Protein Isoforms/blood , Protein Isoforms/chemistry , Vascular Endothelial Growth Factor A/chemistry , Vascular Malformations/blood , Vascular Malformations/complications , Young AdultABSTRACT
OBJECTIVE: To investigate the genetic association of eight variants of the adiponectin gene with type 2 diabetes mellitus (T2DM), obesity and serum adiponectin level in the south Indian population. METHODS: The study comprised of 1100 normal glucose tolerant (NGT) and 1100 type 2 diabetic, unrelated subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Fasting serum adiponectin levels were measured by radioimmunoassay. The variants were screened by polymerase chain reaction-restriction fragment length polymorphism. Linkage disequilibrium was estimated from the estimates of haplotype frequencies. RESULTS: Of the 8 variants, four SNPs namely, +276 G/T (rs1501299), -4522 C/T (rs822393), -11365 C/G (rs266729), and +712 G/A (rs3774261) were significantly associated with T2DM in our study population. The -3971 A/G (rs822396) and -11391 G/A (rs17300539) SNPs' association with T2DM diabetes was mediated through obesity (where the association with type 2 diabetes was lost after adjusting for BMI). There was an independent association of +276 G/T (rs1501299) and -3971 A/G (rs822396) SNPs with generalized obesity and +349 A/G (rs2241767) with central obesity. Four SNPs, -3971 A/G (rs822396), +276 G/T (rs1501299), -4522 C/T (rs822393) and Y111H T/C (rs17366743) were significantly associated with hypoadiponectinemia. The haplotypes GCCATGAAT and AGCGTGGGT conferred lower risk of T2DM in this south Indian population. CONCLUSION: The adiponectin gene variants and haplotype contribute to the genetic risk towards the development of type 2 diabetes, obesity and hypoadiponectinemia in the south Indian population.
Subject(s)
Adiponectin/genetics , Diabetes Mellitus, Type 2/genetics , Obesity, Abdominal/genetics , Polymorphism, Single Nucleotide , Adiponectin/blood , Adult , Case-Control Studies , Diabetes Mellitus, Type 2/blood , Female , Gene Frequency , Genetic Association Studies , Haplotypes , Humans , India , Linkage Disequilibrium , Male , Middle Aged , Obesity, Abdominal/blood , Quantitative Trait, Heritable , Risk Factors , Sequence Analysis, DNAABSTRACT
AIM: The aim of this study was to investigate the association of four variants of the hepatic lipase (HL [or LIPC]) gene with various lipid parameters among South Indian subjects with normal glucose tolerance (NGT). SUBJECTS AND METHODS: In total, 747 NGT subjects were randomly selected from the Chennai Urban Rural Epidemiological Study (CURES). Serum triglycerides, serum cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured using a Hitachi-912 autoanalyzer (Roche Diagnostics GmbH, Mannheim, Germany). Genotyping of HL gene variants was done by the polymerase chain reaction-restriction fragment length polymorphism method, and 20% of samples were sequenced to validate the genotypes obtained. Haplotype analysis was also carried out. RESULTS: The TT genotype of the rs1800588 C/T (C-480T) polymorphism was significantly associated with hypertriglyceridemia, with an adjusted odds ratio of 2.58 (95% confidence interval 1.38-4.85, P=0.003), whereas those with the CC genotype of the rs6074 A/C (Thr479Thr) had significantly lower HDL-C levels (41.3±9.8 mg/dL) compared with the AA genotype (43.6±10.2 mg/dL, P=0.02). Haplotype analysis showed the TGC haplotype was significantly associated with low HDL-C levels. CONCLUSIONS: Among South Indian subjects without diabetes, the rs1800588 C/T (C-480T) and rs6074 C/A (Thr479Thr) variants of the HL gene are associated with hypertriglyceridemia and low HDL-C, respectively. The TGC haplotype was significantly associated with low HDL-C.
