University of Khartoum

Genetic polymorphism and other risk factors as determinants for dyslipidemia among females

Genetic polymorphism and other risk factors as determinants for dyslipidemia among females

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Title: Genetic polymorphism and other risk factors as determinants for dyslipidemia among females
Author: Abdelbasit, Nazik Eltayeb Mohamed
Abstract: Background: There were formidable associations between host genes, life style (diet, obesity and physical activity) and hyperlipidemia. It has been postulated that low density lipoprotein receptor (LDLR), cholesterol ester transfer protein (CETP) and Apo lipoprotein B (ApoB) genes polymorphism could be influencing development of metabolic syndrome in women with hypercholesterolemia. Objectives: This study aimed to identify genetic mutations in low density lipoprotein receptor (LDLR), cholesterol ester transfer protein (CETP) and Apo lipoprotein B (ApoB) genes among Saudi females with metabolic syndrome and dyslipidemia. . Methods: A case control study was conducted. One hundred fifty six (156) females of 104 cases and 52 age matched controls. Cases were obese, diabetics and hypertensive (i. e. with MS), while controls were of normal weight, normal lipid profile, normoglycemic without menstrual irregularities. Anthropometric data included body mass index and waist circumference were collected using a questionnaire. Also fasting venous blood samples were collected from all subjects after informed consent and used for biochemical (blood glucose, lipid profile, leptin and total testosterone). For mutation analysis blood samples were collected for DNA extraction. Specific primers were designed and used for amplification of LDLR gene exon-4, CETP gene intron 1 (segment 1&2) and apoB gene (rsR3500Q, rs693 and rs1801701) mutations using conventional PCR. This was followed by DNA sequencing was done using Capillary Sanger method. Chromatogram files were cleaned and aligned by Finch TV and BioEdit Software program. Chromatograms ABI files variations were searched by Gene Screen program. Finally, Project Hope predicted the effect of the mutations on the structure and function of the protein. Results: The mean BMI and WC for cases were 41.97 (±6.004) and 107.5 centimeters (± 11.68), (p=0.0001) and that for controls were 24.67 for BMI (±2.67), and 69.94 centimeters (±7.85), (p=0.004) for waist circumference. Mean diastolic blood pressure was 86.5 mm/Hg (±1.53) among cases and 74.66 mm/Hg (±1.96) among controls, (p=0.0001). Searching for different variation nucleotides in chromatogram files identified 29 novel mutations in LDLR exon-4, five SNPs within CETP gene intron1 segment -1- and one SNP within segment -2- of CETP gene. ApoB nucleotide sequence gene rsR3500Q (c.10708G>A;p.R3500Q) resulted in no single nucleotide polymorphisms (SNPs) (substitution) within exon 26. apoB gene rs693 (c.7545C>T;p.T2515T) reveald 2 SNPs and apoB gene rs1801701 (c.10913G.A;p.R3638Q) resulted in 2 SNPs. The mean FBG was 162.5 (±6.51) among cases and 66.29 (±4.37), (p=0.0001) for controls. Lipid profile including TG, TC, LDL-C and HDL-C were 204.5 mg/dl (±11.83), 232.5 mg/dl (±10.11), 150.5 mg/dl (±13.51) and 53.2 mg/dl (±8.94) for cases and 67.86 mg/dl (±6.16), 115.9 mg/dl (±8.67), 108.2 mg/dl (±11.83) and 98.67 mg/dl (±6.74) among the control group, the differences were statistically significant (p=0.0001). The mean testosterone and leptin concentrations were found to be 2.00 ng/ml (±0.31) and 27.95 ng/ml (±3.62) within cases and 1.05ng/ml (±0.10) and 5.22 (±1.38) among controls respectively. Statistically significant (p=0.0001) variation between cases and controls were observed for these biochemical and hormonal parameters. Conclusion: This study confirmed that large number of different mutations in the LDLR gene were present among cases due to diversity regarding race and ethnic origin of Makkah population and therefore, the presence of heterogeneity of mutations in LDLR gene. Five different SNPs were detected within intron 1 of CETP. Complete absence of apoB rsR3500Q when investigated. However, the most significant finding was polymorphisms of rs693 (7545C>T) and rs1801701 (c.10913G>A; p.R3638Q) in apoB exon 26. This exon 26 SNPs were known to be associated with high levels of TGs.
URI: http://khartoumspace.uofk.edu/123456789/27165


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