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

Along with rapid global population aging, the age-related cognitive disorders such as mild cognitive impairment (MCI) and dementia have posed a serious threat to public health, health care system, and sustainable economic and societal development of all countries. In this narrative review, we seek to summarize the major epidemiological studies from the life-course perspective that investigate the influence of genetic susceptibility [e.g., apolipoprotein (APOE) e4 allele] and intellectual or psychosocial factors (e.g., educational attainments and leisure activities) as well as their interactions on cognitive phenotypes in aging. Numerous population-based studies have suggested that early-life educational attainments and socioeconomic status, midlife work complexity and social engagements, late-life leisure activities (social, physical, and mentally-stimulating activities), certain personality traits (e.g., high neuroticism and low conscientiousness), and depression significantly affect late-life cognitive phenotypes. Furthermore, certain intellectual or psychosocial factors (e.g., leisure activities and depression) may interact with genetic susceptibility (e.g., APOE e4 allele) to affect the phenotypes of cognitive aging such that risk or beneficial effects of these factors on cognitive function may vary by carrying the susceptibility genes. Current evidence from the randomized controlled trials that support the cognitive benefits of cognitive training among cognitive healthy older adults remains limited. The cognitive reserve hypothesis has been proposed to partly explain the beneficial effects of lifetime intellectual and psychosocial factors on late-life cognitive function. This implies that, from a life-course perspective, preventive intervention strategies targeting multiple modifiable intellectual and psychosocial factors could interfere with clinical expression of cognitive disorders in old age and delay the onset of dementia syndrome, and thus, may help achieve healthy brain aging.

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Lifespan Intellectual Factors, Genetic Susceptibility, and Cognitive Phenotypes in Aging: Implications for Interventions.

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.

Summary.Lipoproteins and vascular factors may play roles in the development of Alzheimer’s disease (AD) and/or vascular dementia (VaD). In this study, odd ratios (ORs) and 95% confidence intervals (CIs) for apolipoprotein E (APOE), angiotensin-converting enzyme (ACE), and kallikrein (KLK1) polymorphisms were computed to test their association with the disease by a case-control study. The risk of AD was significantly increased for individuals with APOE ɛ4 allele (OR = 3.73, 95% CI = 2.38–5.98). The risk of AD was also significant for people with ACE DD genotype, D allele, or T-D haplotype [OR (95% CI) = 4.29 (1.96–10.23), 1.90 (1.35–2.70), or 2.91 (1.71–5.10), respectively]. The above association between ACE-VaD was also strong (p = 0.0012, 0.0050, 0.0007, respectively). Reporter constructs containing the −240 A or T allele displayed similar transcriptional activity in both HEK-293 and IMR-32 cells. Thus, another putative pathogenic marker that is linked with the Alu D allele might affect the risk of AD and VaD in Taiwan.

Apolipoprotein E, angiotensin-converting enzyme and kallikrein gene polymorphisms and the risk of Alzheimer＇s disease and vascular dementia

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.

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

PURPOSE Dementia is a multifactorial idiopathic pathology caused by clinical, eDementia is a multifactorial idiopathic pathology caused by clinical, environmental and genetic factors. Hence, its etiology is still unknown. We aimed to evaluate the association between five genetic risk factors for vascular diseases and dementia individually and when gathered in haplotypes. MATERIALS AND METHOD We enrolled 200 dementia patients and 300 controls. All subjects were genotyped for vascular diseaseassociated polymorphisms in the genes coding for Apolipoprotein-E (ApoE), angiotensin converting enzyme (ACE) and Paraoxonase-1 (PON1). RESULTS The association between dementia risk and all the studied polymorphisms except of PON1-Q192R was found to be significant. Carrying the ApoE e4 allele seems to increase dementia risk by 4.32 fold (p = 0.001). The risk associated with ACE I and PON1-L55M T alleles were lower (2.58 and 2.11 fold, p < 0.001 and p = 0.015, respectively). When combined in haplotypes, these polymorphisms showed a cumulative and synergetic effect. GTICC haplotype appears to be associated with 9-fold dementia risk (p < 0.001), whereas AADTT seems to reduce dementia risk by 80% (p = 0.003). CONCLUSION Our results suggest that, ApoE e4, ACE I and PON1-L55M T alleles are associated with dementia risk whether these polymorphisms were studied separately or gathered in haplotypes. Still, the contribution of each gene to the pathophysiological development of dementia must be more investigated.

Rejeb Jihéne

Papers

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

Association between dementia and vascular disease-associated polymorphisms in a Tunisian population