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      DNA Polymorphisms of the Lipoprotein Lipase Gene and Their Association with Coronary Artery Disease in the Saudi Population

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          Abstract

          Coronary heart disease (CHD) is a major health problem and a major cause of death in most countries. Evidence has been presented that gene polymorphisms ( HindIII, PvuII and Ser447Ter) of lipoprotein lipase (LPL) are risk factors of coronary artery disease (CAD).

          Aim

          Our objective of the present investigation was to determine whether 3 LPL polymorphisms (LPL- HindIII, LPL- PvuII and LPL-Ser447Ter) can be considered as independent risk factors for CAD in the Saudi population.

          Methods

          We recruited 120 CAD subjects, confirmed angiographically with identical ethnic backgrounds and 65 control subjects. Polymerase chain reaction-restriction fragment length polymorphisms (RFLP) technique was used to detect the polymorphisms of the LPL gene.

          Results and conclusion

          For the HindIII genotype, within the CAD group, the frequencies of the H +H + were found in 50.8%, whereas 44.2% carried the H H + genotype, and 5% carried the H H genotype. Within the control group, the H +H + genotype was found in 44.6%, whereas 35.4% carried the H H + genotype, 20% carried the H H genotype. The odds ratio (OR) of HindIII genotype H +H + vs. H H genotype at 95% Confidence Interval (CI) were 4.6 (1.57–13.2) and p < 0.005, hence showing no significant association with CAD. For the PvuII genotype, within the CAD group the frequencies of the P +P + found in 41.7% whereas 43.3.2% carried the P P + genotype, and 15% carried the P P genotype. Within the control group the P +P + was found in 38.5%, 43.0% carried the P P + genotype, and 18.5% carried the P P genotype. The OR of PvuII genotype P +P + vs. P P genotypes (95% CI) is 1.33 and p = 0.52; hence, it was also insignificant to show association with the disease. For the Ser447Ter genotype, within the CAD group, the frequencies of the C/C found in 83.3%, whereas 16.7% carried the C/G genotype. Within the control group, the C/C was found in 87.7% and 12.3% carried the C/G genotype. We did not get any GG genotypes in control as well as patients for this gene. It can be concluded that C allele of gene masks the presence of G allele in the Saudi population. The OR of CG + GG vs. CC (95% CI) is 1.43 from 0.59 to 3.44 which is insignificant. Hence this gene also has no significant association with CAD in the Saudi population.

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          Most cited references38

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          Cardiovascular disease.

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            Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene.

            Patients with lipoprotein lipase deficiency usually present with chylomicronemia in childhood. The syndrome has been considered nonatherogenic primarily because of the low levels of low-density lipoprotein (LDL) cholesterol. We prospectively evaluated patients with lipoprotein lipase deficiency for atherosclerosis. Evidence of carotid, peripheral, and coronary atherosclerosis was sought in four patients (two men and two women) with the phenotype of familial chylomicronemia by clinical examination over a period of 14 to 30 years and by Doppler ultrasonography, B-mode ultrasonography [corrected], and exercise-tolerance testing after the age of 40. Angiography was performed when indicated. Lipoprotein lipase deficiency was assessed in vivo and in vitro by functional assays and DNA-sequence analysis. All four patients had a profound functional deficiency of lipoprotein lipase with a reduced enzymatic mass due to missense mutations on both alleles of the lipoprotein lipase gene. In all four patients, peripheral or coronary atherosclerosis (or both) was observed before the age of 55. Despite following a low-fat diet in which fat composed 10 to 15 percent of the daily caloric intake, the patients had hypertriglyceridemia (mean [+/- SD] triglyceride level, 2621 +/- 1112 mg per deciliter [29.59 +/- 12.55 mmol per liter]), low plasma levels of high-density lipoprotein cholesterol (17 +/- 7 mg per deciliter [0.43 +/- 0.18 mmol per liter]), and very low levels of LDL cholesterol (28 +/- 16 mg per deciliter [0.72 +/- 0.41 mmol per liter]). Three patients had one risk factor for atherosclerosis, whereas in one male patient, heavy smoking and diabetes were associated with an accelerated course of the disease. Premature atherosclerosis can occur in patients with familiar chylomicronemia as a result of mutations in the lipoprotein lipase gene. Defective lipolysis may increase susceptibility to atherosclerosis in humans.
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              Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A meta-analysis.

              We assessed in meta-analyses the effect of the Gly188Glu, Asp9Asn, Asn291Ser, and Ser447Ter substitutions in lipoprotein lipase in the heterozygous state on lipid metabolism and risk of ischemic heart disease (same order used below). In 29 separate studies, 20 903 white subjects were screened for >/=1 of these substitutions; each meta-analysis included only some of these individuals. In population-based studies, heterozygote frequencies ranged from 0.04% to 0.2%, 2% to 4%, 1% to 7%, and 17% to 22% for the respective substitutions. Postheparin plasma lipoprotein lipase activity decreased 53% (95% CI, 31% to 75%) (only 1 study), 30% (22% to 37%), and 22% (8% to 35%) and was unchanged at 4% (-10% to 19%), respectively. Plasma triglycerides increased 78% (95% CI, 64% to 92%), 20% (9% to 33%), and 31% (20% to 43%) and decreased 8% (4% to 11%), respectively. HDL cholesterol decreased 0. 25 mmol/L (0.18 to 0.32), 0.08 mmol/L (0.04 to 0.12), and 0.12 mmol/L (0.10 to 0.15) and increased 0.04 mmol/L (0.02 to 0.06), respectively. Odds ratios for ischemic heart disease were 4.9 (95% CI, 1.2 to 20) (only 1 study), 1.4 (0.8 to 2.4), 1.2 (0.9 to 1.5), and 0.8 (0.7 to 1.0), respectively. Subgroup analysis indicated that women with the Asn291Ser substitution may have an increased risk of ischemic heart disease. These meta-analyses suggest that compared with noncarriers, carriers of the Gly188Glu, Asp9Asn, and Asn291Ser substitutions have an atherogenic lipoprotein profile, whereas carriers of the Ser447Ter substitution have a protective lipoprotein profile. Accordingly, risk of ischemic heart disease in heterozygous carriers is increased for Gly188Glu carriers; at most, the increase is borderline for Asp9Asn and Asn291Ser carriers; and risk is possibly decreased for Ser447Ter carriers.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                Molecular Diversity Preservation International (MDPI)
                1422-0067
                2012
                18 June 2012
                : 13
                : 6
                : 7559-7574
                Affiliations
                [1 ]Department of Biochemistry, Faculty of Science, King Saud University, 11451, Saudi Arabia; E-Mails: dr_mohamed301@ 123456hotmail.com (M.S.D.); msanazi@ 123456ksu.edu.sa (M.S.A.A.)
                [2 ]Cardiac Sciences Department, Faculty of Medicine, King Saud University, 11472, Saudi Arabia; E-Mail: amobeirek@ 123456yahoo.com
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: ajafari@ 123456ksu.edu.sa ; Tel.: +966-1-4675953; Fax: +966-1-4675791.
                Article
                ijms-13-07559
                10.3390/ijms13067559
                3397544
                22837712
                ea9f8025-83fe-4a78-80b4-315eec3ed5f7
                © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 20 March 2012
                : 30 May 2012
                : 08 June 2012
                Categories
                Article

                Molecular biology
                restrictions fragment,lipoprotein lipase,saudi populations and polymorphism,coronary artery disease,genotypes

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