Coronary artery disease

This is the oldest English language journal in genetics. Founded by W. Bateson and R. C. Punnett in 1910, the Journal of Genetics was later edited by J. B. S. Haldane; later, Haldane and his wife, Helen Spurway brought the journal with them to India. After his death in 1964, Mrs. Haldane continued publication of the journal, with Madhav Gadgil and H. Sharat Chandra (Indian Institute of Science, Bangalore) and Suresh Jayakar (Laboratorio de Genetica Biochimica ed Evoluzionistica, Pavia) as editors, until her own death in 1977. In 1985, with the permission of Haldane’s heirs, the Indian Academy of Sciences resumed publication of the journal. The journal retains its traditional interest in evolutionary research that is of relevance to geneticists, even if not explicitly genetic in nature.

The journal of genetics

The associations of the apolipoprotein B gene (APOB) rs693 and rs17240441 polymorphisms with plasma levels of APOB and lipids have been widely explored, but the results were inconclusive. This meta-analysis aimed to clarify the associations of the rs693 and rs17240441 polymorphisms with fasting APOB and lipid levels. Sixty-one studies (50,018 subjects) and 23 studies (8425 subjects) were respectively identified for the rs693 and rs17240441 polymorphisms by searching in PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang, VIP and CNKI databases. The following information was collected for each study: first author, age, gender, ethnicity, health condition, sample size, genotyping, lipid assay method, mean and standard deviation or standard error of APOB and lipid variables by genotypes. A dominant model was used for this meta-analysis. The carriers of the rs693 variant allele (T) had higher levels of APOB [standardized mean difference (SMD) = 0.26, 95% confidence interval (CI) = 0.16–0.36, P < 0.01], triglycerides (TG) (SMD = 0.12, 95% CI = 0.05–0.20, P < 0.01), total cholesterol (TC) (SMD = 0.24, 95% CI = 0.17–0.30, P < 0.01) and low-density lipoprotein cholesterol (LDL-C) (SMD = 0.22, 95% CI = 0.14–0.30, P < 0.01), and lower levels of high-density lipoprotein cholesterol (HDL-C) (SMD = −0.06, 95% CI = −0.11–0.01, P = 0.01) than the non-carriers. The carriers of the rs17240441 deletion allele had higher levels of APOB (SMD = 0.13, 95% CI = 0.06–0.20, P < 0.01), TC (SMD = 0.17, 95% CI = 0.07–0.26, P < 0.01) and LDL-C (SMD = 0.15, 95% CI = 0.07–0.23, P < 0.01) than the non-carriers. The rs693 polymorphism is significantly associated with higher levels of APOB, TG, TC and LDL-C, and lower levels of HDL-C. The rs17240441 polymorphism is significantly associated with higher levels of APOB, TC and LDL-C. Further studies are needed to elucidate the underlying mechanisms.

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Associations of the APOB rs693 and rs17240441 polymorphisms with plasma APOB and lipid levels: a meta-analysis.

Type 2 diabetes mellitus (T2DM) and its complications are linked to environmental, clinical, and genetic factors. This review analyses the disorders of lipids and their genetics with respect to coronary artery disease (CAD) associated with T2DM. Cell organelles, hepatitis C-virus infection, reactive oxygen species produced in mitochondria, and defective insulin signaling due to the arrest of G1 phase to S phase transition of β-cells have significant roles in the precipitation of the diseases. Adiponectin is anti-inflammatory and anti-atherosclerotic and improves insulin resistance. Low-density lipoprotein (LDL) is atherosclerotic, and LDL-cholesterol in T2DM is associated with high-cardiovascular risk. Further, LDL cholesterol reduction significantly reduces cardiovascular morbidity and mortality. High-density lipoprotein (HDL) is also anti-atherosclerotic due to HDL associated paraoxonase-1 serum enzyme, which prevents LDL oxidative modifications and the development of CAD. Moreover, elevated apolipoprotein B and apolipoprotein A-I (ApoB/ApoA-I) ratio in plasma is also a risk factor for CAD. LDL receptor, adiponectin, and endocannabinoid receptor-1 genes are independently associated with CAD and T2DM. Polymorphism of Apo E2 (epsilon2) is a positive factor to increase the T2DM risk and Apo E4 (epsilon4) is a negative factor to reduce the disease risk. Taq 1B polymorphism of cholesterol ester transfer protein (CETP) gene contributes to the development of atherosclerosis, whereas haplotypes of APOA5, APOC3, APOC4, and APOC5 genes are in the same cluster and are independently associated with high plasma triglyceride level, CAD and T2DM. In conclusion, because various genes, LDLR, CETP, APOA5, Apo E, Apo B, and Apo A-I, are associated with the precipitation of CAD associated with T2DM, a personalized diet-gene intervention therapy may be advocated to reduce the disease precipitation.

Genetic basis of dyslipidemia in disease precipitation of coronary artery disease (CAD) associated type 2 diabetes mellitus (T2DM).

Many SNPs have been identified in genes regulating LDL-C metabolism, but whether their influence is similar in subjects from different ethnicities is unclear. Effect of 4 such SNPs on LDL-C and coronary heart disease (CHD) was examined in Pakistani subjects and was compared with middle aged UK men from Northwick Park Heart Study II (NPHSII). One thousand nine hundred sixty-five (1770 non CHD, 195 CHD) UK and 623 (219 non CHD, 404 CHD) Pakistani subjects were enrolled in the study. The SNPs SORT1 rs646776, APOB rs1042031 and APOE rs429358, rs7412 were genotyped by TaqMan/KASPar technique and their gene score was calculated. LDL-C was calculated by Friedewald equation, results were analyzed using SPSS. Allele frequencies were significantly different (p = <0.05) between UK and Pakistani subjects. However, the SNPs were associated with LDL-C in both groups. In UK non CHD, UK CHD, Pakistani non CHD and Pakistani CHD respectively, for rs646776, per risk allele increase in LDL-C(mmol/l) was 0.18(0.04), 0.06(0.11), 0.15(0.04) and 0.27(0.06) respectively. For rs1042031, per risk allele increase in LDL-C in four groups was 0.11(0.04), 0.04(0.14), 0.15(0.06) and 0.25(0.09) respectively. For APOE genotypes, compared to Ɛ3, each Ɛ2 decreased LDL-C by 0.11(0.06), 0.07(0.15), 0.20(0.08) and 0.38(0.09), while each Ɛ4 increased LDL-C by 0.43(0.06), 0.39(0.21), 0.19(0.11) and 0.39(0.14) respectively. Overall gene score explained a considerable proportion of sample variance in four groups (3.8 %, 1.26 % 13.7 % and 12.3 %). Gene score in both non-CHD groups was significantly lower than CHD subjects. The SNPs show a dose response association with LDL-C levels and risk of CHD in both populations.

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Effect of SORT1 , APOB and APOE polymorphisms on LDL-C and coronary heart disease in Pakistani subjects and their comparison with Northwick Park Heart Study II

Numerous studies have shown that apolipoprotein B (APOB) is a better predictor of cardiovascular disease (CVD) risk than low-density lipoprotein C (LDL-C). We studied the following four polymorphisms in APOB gene: 5′ins/del polymorphism (rs17240441), 3′VNTR polymorphism, XbaI polymorphism (rs693) and the EcoRI polymorphism (rs1042031). The association of these four polymorphisms with lipid variation and CVD risk have been controversial (Bøhn et al. 1994; Pan et al. 1998; Duman et al. 2005; Kallel et al. 2007; Rebhi et al. 2008). The aim of this study was to investigate the association of these four polymorphisms and haplotypes with significant coronary stenosis (SCS), coronary artery disease (CAD) and lipid parameters in a Tunisian population.

Kacem Slim

Papers

Association of four apolipoprotein B polymorphisms with lipid profile and stenosis in Tunisian coronary patients.