Vascular Genetic Variants and Ischemic Stroke Susceptibility in Albanians from the Republic of Macedonia

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Abstract

BACKGROUND:

Acute first-ever ischemic stroke (FIS) is a heterogeneous, polygenic disorder. The contribution of vascular genetic variants as inherited causes of ischemic stroke has remained controversial.

AIM:

To examine the association of genetic variants in vascular factors with the occurrence of FIS.

MATERIAL AND METHODS:

The current research was performed in a group of 39 patients with FIS (study group) and 102 healthy volunteers (control group). We analyzed the prevalence of vascular genetic variants in following genes: factor V, prothrombin, methylenetetrahydrofolate reductase (MTHFR), factor XIII, plasminogen activator 1, endothelial protein C receptor (EPCR), apolipoprotein B, apolipoprotein E, β-fibrinogen, human platelet antigen 1, angiotensin-converting enzyme (ACE), endothelial nitric oxide synthase (eNOS) and lymphotoxin alpha.

RESULTS:

It was found that heterozygous LTA 804C>A and FXIII V34L Leu/Leu were significantly more frequent in patients with FIS than in control group (p = 0.036 and p = 0.017, respectively). The frequency of FXIII V34L Val/Val was significantly lower in patients with FIS than in control group (p = 0.020). Other frequencies of vascular gene variants in patients with FIS and in control group were not significantly different.

CONCLUSIONS:

This is the first comprehensive study to present data indicating that polymorphism of vascular genes in the prevalence of acute FIS exists in the Albanian population from the Republic of Macedonia. Variations in these genes have been detected in patients with acute FIS, suggesting that their combination might act in a susceptible or protective manner in this Albanian population.

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Most cited references 77

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Lifetime risks of cardiovascular disease.

Jarett D Berry, Alan Dyer, Xuan Cai … (2012)

The lifetime risks of cardiovascular disease have not been reported across the age spectrum in black adults and white adults. We conducted a meta-analysis at the individual level using data from 18 cohort studies involving a total of 257,384 black men and women and white men and women whose risk factors for cardiovascular disease were measured at the ages of 45, 55, 65, and 75 years. Blood pressure, cholesterol level, smoking status, and diabetes status were used to stratify participants according to risk factors into five mutually exclusive categories. The remaining lifetime risks of cardiovascular events were estimated for participants in each category at each age, with death free of cardiovascular disease treated as a competing event. We observed marked differences in the lifetime risks of cardiovascular disease across risk-factor strata. Among participants who were 55 years of age, those with an optimal risk-factor profile (total cholesterol level, <180 mg per deciliter [4.7 mmol per liter]; blood pressure, <120 mm Hg systolic and 80 mm Hg diastolic; nonsmoking status; and nondiabetic status) had substantially lower risks of death from cardiovascular disease through the age of 80 years than participants with two or more major risk factors (4.7% vs. 29.6% among men, 6.4% vs. 20.5% among women). Those with an optimal risk-factor profile also had lower lifetime risks of fatal coronary heart disease or nonfatal myocardial infarction (3.6% vs. 37.5% among men, <1% vs. 18.3% among women) and fatal or nonfatal stroke (2.3% vs. 8.3% among men, 5.3% vs. 10.7% among women). Similar trends within risk-factor strata were observed among blacks and whites and across diverse birth cohorts. Differences in risk-factor burden translate into marked differences in the lifetime risk of cardiovascular disease, and these differences are consistent across race and birth cohorts. (Funded by the National Heart, Lung, and Blood Institute.).

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Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: the Helsinki young stroke registry.

Jukka Putaala, Antti J Metso, Tiina Metso … (2009)

To analyze trends in occurrence, risk factors, etiology, and neuroimaging features of ischemic stroke in young adults in a large cohort. We evaluated all 1008 consecutive ischemic stroke patients aged 15 to 49 admitted to Helsinki University Central Hospital, 1994 to 2007. Etiology was classified by Trial of Org 10172 in Acute Stroke Treatment criteria. Comparisons were done between groups stratified by gender and age. Estimated annual occurrence was 10.8/100,000 (range 8.4 to 13.0), increasing exponentially with aging. Of our 628 male and 380 female (ratio 1.7:1) patients, females were preponderant among those 44 clearly had more risk factors. Cardioembolism (20%) and cervicocerebral artery dissection (15%) were the most frequent etiologic subgroups. Proportions of large-artery atherosclerosis (8%) and small-vessel disease (14%) began to enlarge at age 35, whereas frequency of undetermined etiology (33%) decreased along aging. Posterior circulation infarcts were more common among patients <45 years of age. Left hemisphere infarcts were more frequent in general. There were 235 (23%) patients with multiple and 126 (13%) with silent infarcts, and 55 (5%) patients had leukoaraiosis. The frequency of ischemic stroke increases sharply at age 40. Etiology and risk factors start resembling those seen in the elderly in early midlife but causes defined in younger patients still are frequent in those aged 45 to 49. Subclinical infarcts were surprisingly common in the young.

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Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction.

Akihiko Sekine, Hiroshi Sato, Masatsugu Hori … (2002)

By means of a large-scale, case-control association study using 92,788 gene-based single-nucleotide polymorphism (SNP) markers, we identified a candidate locus on chromosome 6p21 associated with susceptibility to myocardial infarction. Subsequent linkage-disequilibrium (LD) mapping and analyses of haplotype structure showed significant associations between myocardial infarction and a single 50 kb halpotype comprised of five SNPs in LTA (encoding lymphotoxin-alpha), NFKBIL1 (encoding nuclear factor of kappa light polypeptide gene enhancer in B cells, inhibitor-like 1) and BAT1 (encoding HLA-B associated transcript 1). Homozygosity with respect to each of the two SNPs in LTA was significantly associated with increased risk for myocardial infarction (odds ratio = 1.78, chi(2) = 21.6, P = 0.00000033; 1,133 affected individuals versus 1,006 controls). In vitro functional analyses indicated that one SNP in the coding region of LTA, which changed an amino-acid residue from threonine to asparagine (Thr26Asn), effected a twofold increase in induction of several cell-adhesion molecules, including VCAM1, in vascular smooth-muscle cells of human coronary artery. Moreover, the SNP, in intron 1 of LTA, enhanced the transcriptional level of LTA. These results indicate that variants in the LTA are risk factors for myocardial infraction and implicate LTA in the pathogenesis of the disorder.

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Author and article information

Journal

Journal ID (nlm-ta): Open Access Maced J Med Sci

Journal ID (iso-abbrev): Open Access Maced J Med Sci

Title: Open Access Macedonian Journal of Medical Sciences

Publisher: Institute of Immunobiology and Human Genetics (Republic of Macedonia )

ISSN (Electronic): 1857-9655

Publication date (Print): 15 December 2016

Publication date (Electronic): 01 October 2016

Volume: 4

Issue: 4

Pages: 556-564

Affiliations

[1 ] Neurological Department, Clinical Hospital, Tetovo, Republic of Macedonia

[2 ] School Medical Centre, “Nikolla Shtejn” Tetovo, Republic of Macedonia

[3 ] Institute of Immunobiology and Human Genetics, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia

Author notes

[* ] Correspondence: Bajram Kamberi, MD, PhD. Department of Neurology, Clinical Hospital Tetovo, 1200 Tetovo, Republic of Macedonia. Tel: (+389 44) 72 239 014, E-mail: bajram-kamberi@ 123456yahoo.com

Article

Publisher ID: OAMJMS-4-556

DOI: 10.3889/oamjms.2016.114

PMC ID: 5175499

SO-VID: 3651a4f5-d5fc-41fd-9b9e-e84204bc3fa5

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).

History

Date received : 01 July 2016

Date revision received : 26 September 2016

Date accepted : 28 September 2016

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Vascular Genetic Variants and Ischemic Stroke Susceptibility in Albanians from the Republic of Macedonia

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Abstract

BACKGROUND:

AIM:

MATERIAL AND METHODS:

RESULTS:

CONCLUSIONS:

Related collections

Vascular Biology

Most cited references 77

Lifetime risks of cardiovascular disease.

Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: the Helsinki young stroke registry.

Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction.

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Cited by 3

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