Association of Genes Related to Oxidative Stress with the Extent of Coronary Atherosclerosis

Oxidative stress is believed to play a critical role in atherosclerosis initiation and progression. In line with this, in a group of 1099 subjects, we determined eight single nucleotide polymorphisms (SNPs) related to oxidative stress (PON1 c.575A>G, MPO c.−463G>A, SOD2 c.47T>C, GCLM c.−590C>T, NOS3 c.894G>T, NOS3 c.−786T>C, CYBA c.214C>T, and CYBA c.−932A>G) and assessed the extent of atherosclerosis in coronary arteries based on Gensini score. An increased risk of having a Gensini score in the higher half of the distribution was observed for the PON1 c.575G allele (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.004–1.617, p = 0.046). Next, the genetic risk score (GRS) for the additive effect of the total number of pro-oxidative alleles was assessed. We noted an increase in the risk of having a Gensini score above the median with the maximum number of risk alleles (OR = 2.47, 95% CI: 1.19–5.23, p = 0.014). A univariate Spearman’s test revealed significant correlation between the total number of pro-oxidant alleles (GRS) and the Gensini score (ρ = 0.068, p = 0.03). In conclusion, the PON1 c.575A>G variant and the high number of risk alleles (GRS) were independent risk factors for a high Gensini score. We suggest, however, that GRS might occur as a more valuable component in adding a predictive value to the genetic background of atherosclerosis.

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The association of adiponectin gene polymorphisms with susceptibility and progression of NAFLD in a cohort of Egyptian patients

Egyptian Liver Journal ◽

10.1186/s43066-021-00103-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eman M. Hasan ◽

Rasha A. Abd Al Aziz ◽

Dina Sabry ◽

Hedy A. Badary ◽

Yasmine Gaber ◽

...

Keyword(s):

Multivariate Regression ◽

Multivariate Regression Analysis ◽

Nucleotide Polymorphisms ◽

Adiponectin Gene ◽

Single Nucleotide ◽

Alcoholic Fatty Liver ◽

Increased Risk ◽

Egyptian Patients ◽

Independent Risk Factors ◽

Alcoholic Fatty Liver Disease

Abstract Background Several genetic polymorphisms have been proven to play a key role in the progression of non-alcoholic fatty liver disease (NAFLD) from simple steatosis to NASH with fibrosis. Our aim was to study the effect of single nucleotide polymorphisms (SNPs) in the adiponectin gene, namely rs266729 and rs3774261, on susceptibility to NAFLD and disease progression. Results There was a definitive association between polymorphisms of the studied SNPs and NAFLD. Among rs266729, CG was significantly higher among patients than controls showing increased risk for NAFLD (P<0.05). AA genotype of the rs3774261 variant was significantly lower in patients than in controls (P value< 0.001) while AG and GG genotypes were significantly higher in patients than in controls (P value<0.05); A allele was significantly higher among controls (P=0.019) which might have a protective effect. None of the variants correlated significantly with the degree of steatosis. Using multivariate regression analysis, there was no significant correlation with any of the independent risk factors to the degree of steatosis. Conclusions There was an association between polymorphisms of the studied SNPs of rs266729 and rs3774261 of the adiponectin gene and NAFLD.

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Joint effect of multiple prothrombotic genotypes and obesity on the risk of incident venous thromboembolism

Thrombosis and Haemostasis ◽

10.1055/a-1497-9777 ◽

2021 ◽

Author(s):

Tobias Frischmuth ◽

Kristian Hindberg ◽

Maiken Elvestad Gabrielsen ◽

Ben Michael Brumpton ◽

Kristian Hveem ◽

...

Keyword(s):

Venous Thromboembolism ◽

Genetic Risk Score ◽

Joint Effect ◽

Additive Effect ◽

Health Study ◽

Nucleotide Polymorphisms ◽

Risk Alleles ◽

Individual Snps ◽

Increased Risk ◽

The Impact

Background: The impact of the combination of obesity and multiple prothrombotic genotypes on venous thromboembolism (VTE) risk remains unclear. Objective: To investigate the joint effect of obesity and a genetic risk score (GRS) comprised of established prothrombotic single nucleotide polymorphisms (SNPs) on VTE risk using a population-based case-cohort. Methods: Cases with incident VTE (n=1,470) and a subcohort (n=12,826) were derived from the Tromsø Study (1994‐2012) and the Trøndelag Health Study (HUNT) (1995‐2008). Participants were genotyped for ABO (rs8176719), F5 (rs6025), F2 (rs1799963), FGG (rs2066865) and F11 (rs2036914) SNPs. Age- and sex-adjusted hazard ratios (HRs) were estimated according to body mass index (BMI) categories and number of risk alleles for individual SNPs and the GRS (0-1, 2, 3, ≥4 alleles). Results: The combination of obesity (BMI≥30kg/m2) and risk alleles, either as individual SNPs or as a GRS, had an additive effect on VTE risk (i.e. no biological interaction). Obese subjects who were carriers of ≥4 risk alleles had a 2.85-fold (95% confidence intervals [CI] 2.05-3.96) increased risk of overall VTE compared to those with BMI<25kg/m2 and 0-1 risk allele. However, in subgroups, the combination of obesity and ≥4 risk alleles was more pronounced for deep vein thrombosis (DVT) (HR 3.20, 95% CI 2.09-4.90) and unprovoked VTE (HR 3.82, 95% CI 2.25-6.47), suggesting a supra-additive effect. Conclusion: Our findings indicate that the combination of obesity and GRS has an additive effect on the risk of overall VTE. However, it may have a supra-additive effect on the risk of DVT and unprovoked VTE.

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Genetic Variants in KIR/HLA-C Genes Are Associated With the Susceptibility to HCV Infection in a High-Risk Chinese Population

Frontiers in Immunology ◽

10.3389/fimmu.2021.632353 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chao Shen ◽

Zhijun Ge ◽

Chen Dong ◽

Chunhui Wang ◽

Jianguo Shao ◽

...

Keyword(s):

High Risk ◽

Chinese Population ◽

Drug Users ◽

Hcv Infection ◽

Taqman Assay ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Risk Alleles ◽

Increased Risk ◽

Control Study

BackgroundKIR/HLA-C signaling pathway influences the innate immune response which is the first defense to hepatitis C virus (HCV) infection. The aim of this study was to determine the association between the genetic polymorphisms of KIR/HLA-C genes and the outcomes of HCV infection in a high-risk Chinese population.MethodsIn this case-control study, four single nucleotide polymorphisms (SNPs) of KIR/HLA-C genes (KIR2DS4/KIR2DS1/KIR2DL1 rs35440472, HLA-C rs2308557, HLA-C rs1130838, and HLA-C rs2524094) were genotyped by TaqMan assay among drug users and hemodialysis (HD) patients including 1,378 uninfected control cases, 307 subjects with spontaneous viral clearance, and 217 patients with persistent HCV infection. Bioinformatics analysis was used to functionally annotate the SNPs.ResultsAfter logistic regression analysis, the rs35440472-A and rs1130838-A alleles were found to be associated with a significantly elevated risk of HCV infection (OR = 1.562, 95% CI: 1.229–1.987, P < 0.001; OR = 2.134, 95% CI: 1.180–3.858, P = 0.012, respectively), which remained significant after Bonferroni correction (0.05/4). The combined effect of their risk alleles and risk genotypes (rs35440472-AA and rs1130838-AA) were linked to the increased risk of HCV infection in a locus-dosage manner (all Ptrend < 0.001). Based on the SNPinfo web server, rs35440472 was predicted to be a transcription factor binding site (TFBS) while rs1130838 was predicted to have a splicing (ESE or ESS) function.ConclusionKIR2DS4/KIR2DS1/KIR2DL1 rs35440472-A and HLA-C rs1130838-A variants are associated with increased susceptibility to HCV infection in a high-risk Chinese population.

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Gene polymorphisms associated with an increased risk of exudative age-related macular degeneration in a Spanish population

European Journal of Ophthalmology ◽

10.1177/11206721211002698 ◽

2021 ◽

pp. 112067212110026

Author(s):

Pablo Gili ◽

Leyre Lloreda Martín ◽

José-Carlos Martín-Rodrigo ◽

Naon Kim-Yeon ◽

Laura Modamio-Gardeta ◽

...

Keyword(s):

Macular Degeneration ◽

Gene Polymorphisms ◽

Age Related Macular Degeneration ◽

Spanish Population ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Exudative Amd ◽

Age Related ◽

Increased Risk

Purpose: To identify the association between single-nucleotide polymorphisms (SNPs) in CFH, ARMS2, HTRA1, CFB, C2, and C3 genes and exudative age-related macular degeneration (AMD) in a Spanish population. Methods: In 187 exudative AMD patients and 196 healthy controls (61% women, mean age 75 years), 12 SNPs as risk factors for AMD in CFH (rs1410996, rs1061170, r380390), ARMS2 (rs10490924, rs10490923), HTRA1 (rs11200638), CFB (rs641153), C2 (rs547154, rs9332739), and C3 (rs147859257, rs2230199, rs1047286) genes were analyzed. Results: The G allele was the most frequent in CFH gene (rs1410996) with a 7-fold increased risk of AMD (OR 7.69, 95% CI 3.17–18.69), whereas carriers of C allele in CFH (rs1061170) showed a 3-fold increased risk for AMD (OR 3.22, 95% CI 1.93–5.40). In CFH (rs380390), the presence of G allele increased the risk for AMD by 2-fold (OR 2.52, 95% CI 1.47–4.30). In ARMS2 (rs10490924), the T-allele was associated with an almost 5-fold increased risk (OR 5.49, 95% CI 3.23–9.31). The A allele in HTRA1 (rs11200638) was more prevalent in AMD versus controls (OR 6.44, 95% CI 3.62–11.47). In C2 gene (rs9332739) the presence of C increased risk for AMD by 3-fold (OR 3.10, 95% CI 1.06–9.06). Conclusion: SNPs in CFH, ARMS2, HTRA1, and C2 genes were associated in our study with an increased risk for exudative AMD in Spanish patients.

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miR-146a and miR-196a-2 genes polymorphisms and its circulating levels in lung cancer patients

The Journal of Biochemistry ◽

10.1093/jb/mvz044 ◽

2019 ◽

Vol 166 (4) ◽

pp. 323-329 ◽

Cited By ~ 2

Author(s):

Randa H Mohamed ◽

Heba F Pasha ◽

Doaa M Gad ◽

Mostafa M Toam

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Cancer Patients ◽

Lung Cancer Risk ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Lung Cancer Patients ◽

Increased Risk ◽

Increase Risk ◽

Circulating Levels

AbstractRecently, MicroRNAs polymorphisms and their serum expression have been linked to increase risk of various cancers. The aim of this study was to elucidate the association between single nucleotide polymorphisms of miR-146a and miR-196a-2 and their serum expression and lung cancer risk. One hundred and twenty lung cancer patients and 120 health controls were included in this study. Genotyping and expression for miR-146a and miR-196a-2 were performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and quantitative real-time PCR. Individuals carrying miR-146a CG and CC genotypes had significantly increased risk for lung cancer than those carrying miR-146a GG genotype. MiR-146a expression significantly decreased in miR-146a CG and CC genotypes carriers as compared with GG genotype carriers. MiR-196a-2 CT and TT genotypes were significantly associated with increased lung cancer while the highest expression of MiR-196a-2 was detected in miR-196a-2 CC genotype carriers. Serum miR-146a was significantly decreased in lung cancer patients while serum miR-196a-2 expression was significantly increased in lung cancer patients. In conclusion, miR-146a and miR-196a-2 genes polymorphisms and their circulating levels were associated with lung cancer risk in Egyptians and may be helpful in early detection of lung cancer.

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NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.131243 ◽

2010 ◽

Vol 70 (4) ◽

pp. 668-674 ◽

Cited By ~ 65

Author(s):

P Dieudé ◽

M Guedj ◽

J Wipff ◽

B Ruiz ◽

G Riemekasten ◽

...

Keyword(s):

Innate Immunity ◽

Systemic Sclerosis ◽

Potential Role ◽

Additive Model ◽

Nucleotide Polymorphisms ◽

Fibrosing Alveolitis ◽

Single Nucleotide ◽

Risk Alleles ◽

Caucasian Origin

BackgroundRecent evidence has highlighted a potential role of interleukin 1β (IL-1β) in systemic sclerosis (SSc). NLRP1 provides a scaffold for the assembly of the inflammasome that promotes the processing and maturation of pro-IL-1β. In addition, NLRP1 variants were found to confer susceptibility to autoimmune disorders.ObjectiveTo study a possible association of the NLRP1 rs6502867, rs2670660 and rs8182352, rs12150220 and rs4790797 with SSc in the European Caucasian population.MethodsNLRP1 single nucleotide polymorphisms were genotyped in 3227 individuals comprising a discovery set (870 SSc patients and 962 controls) and a replication set including individuals from Germany (532 SSc patients and 324 controls) and Italy (527 SSc patients and 301 controls), all individuals being of European Caucasian origin.ResultsConditional analyses revealed a significant association for the NLRP1 rs8182352 variant with both anti-topoisomerase-positive and SSc-related fibrosing alveolitis (FA) subsets under an additive model: p=0.0042, OR 1.23 (95% CI 1.07 to 1.41) and p=0.0065 OR 1.19 (95% CI 1.05 to 1.36), respectively. Logistic regression analysis showed an additive effect of IRF5 rs2004640, STAT4 rs7574865 and NLRP1 rs8182352 risk alleles on SSc-related FA.ConclusionsOur results establish NLRP1 as a new genetic susceptibility factor for SSc-related pulmonary fibrosis and anti-topoisomerase-positive SSc phenotypes. This provides new insights into the pathogenesis of SSc, underlining the potential role of innate immunity in particular in the FA-positive SSc subphenotype, which represents a severe subset of the disease.

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Focal segmental glomerulosclerosis is associated with a PDSS2 haplotype and, independently, with a decreased content of coenzyme Q10

AJP Renal Physiology ◽

10.1152/ajprenal.00143.2013 ◽

2013 ◽

Vol 305 (8) ◽

pp. F1228-F1238 ◽

Cited By ~ 24

Author(s):

David L. Gasser ◽

Cheryl A. Winkler ◽

Min Peng ◽

Ping An ◽

Louise M. McKenzie ◽

...

Keyword(s):

Focal Segmental Glomerulosclerosis ◽

Cell Lines ◽

Coenzyme Q ◽

Lymphoblastoid Cell Lines ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Collapsing Glomerulopathy ◽

Segmental Glomerulosclerosis ◽

Increased Risk ◽

Common Causes

Focal segmental glomerulosclerosis (FSGS) and collapsing glomerulopathy are common causes of nephrotic syndrome. Variants in >20 genes, including genes critical for mitochondrial function, have been associated with these podocyte diseases. One such gene, PDSS2, is required for synthesis of the decaprenyl tail of coenzyme Q10 (Q10) in humans. The mouse gene Pdss2 is mutated in the kd/kd mouse model of collapsing glomerulopathy. We examined the hypothesis that human PDSS2 polymorphisms are associated with podocyte diseases. We genotyped 377 patients with primary FSGS or collapsing glomerulopathy, together with 900 controls, for 9 single-nucleotide polymorphisms in the PDSS2 gene in a case-control study. Subjects included 247 African American (AA) and 130 European American (EA) patients and 641 AA and 259 EA controls. Among EAs, a pair of proxy SNPs was significantly associated with podocyte disease, and patients homozygous for one PDSS2 haplotype had a strongly increased risk for podocyte disease. By contrast, the distribution of PDSS2 genotypes and haplotypes was similar in AA patients and controls. Thus a PDSS2 haplotype, which has a frequency of 13% in the EA control population and a homozygote frequency of 1.2%, is associated with a significantly increased risk for FSGS and collapsing glomerulopathy in EAs. Lymphoblastoid cell lines from FSGS patients had significantly less Q10 than cell lines from controls; contrary to expectation, this finding was independent of PDSS2 haplotype. These results suggest that FSGS patients have Q10 deficiency and that this deficiency is manifested in patient-derived lymphoblastoid cell lines.

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Candidate Genes of the 5-Lipoxygenase Pathway in Acute Coronary Syndrome: A Pilot Study

Biological Research For Nursing ◽

10.1177/1099800407313385 ◽

2008 ◽

Vol 9 (4) ◽

pp. 280-292 ◽

Cited By ~ 3

Author(s):

Shu-Fen Wung ◽

Bradley E. Aouizerat

Keyword(s):

Acute Coronary Syndrome ◽

Pilot Study ◽

Nucleotide Polymorphisms ◽

Common Allele ◽

Lipoxygenase Pathway ◽

Single Nucleotide ◽

Coronary Syndrome ◽

Increased Risk ◽

Caucasian Patients ◽

Alox5ap Gene

Purpose. The purpose of this pilot study was to examine arachidonate 5-lipoxygenase (ALOX5) and ALOX5-activating protein (ALOX5AP) gene variations in patients with and without acute coronary syndrome (ACS). Methodology. Four and six single nucleotide polymorphisms spanning the ALOX5 and ALOX5AP genes, respectively, were genotyped in 19 non-Hispanic Caucasian patients with ACS and 27 controls. Results. Presence of the common allele of rs9508835 (ALOX5AP) and the minor allele of rs2029253 (ALOX5) were associated with ACS. After adjustment for age, being a carrier of the rs9508835 common allele was associated with an increased risk of ACS (odds ratio = 2.86). Relevance for nursing practice. Through the inhibition of the ALOX5AP gene by downregulation of the leukotriene pathway, the risk of ACS may be decreased in individuals that carry susceptibility allele(s). Knowledge of the genetic basis of treatments that downregulate the leukotriene pathway may prove essential to the care of individuals with ACS.

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Susceptible genes of restless legs syndrome in migraine

Cephalalgia ◽

10.1177/0333102415620907 ◽

2016 ◽

Vol 36 (11) ◽

pp. 1028-1037 ◽

Cited By ~ 18

Author(s):

Jong-Ling Fuh ◽

Ming-Yi Chung ◽

Shu-Chih Yao ◽

Ping-Kun Chen ◽

Yi-Chu Liao ◽

...

Keyword(s):

Restless Legs Syndrome ◽

Genetic Variants ◽

Multivariate Regression ◽

Iron Homeostasis ◽

Nucleotide Polymorphisms ◽

Regression Analyses ◽

Single Nucleotide ◽

Association Analyses ◽

Restless Legs ◽

Increased Risk

Objective Several genetic variants have been found to increase the risk of restless legs syndrome (RLS). The aim of the present study was to determine if these genetic variants were also associated with the comorbidity of RLS and migraine in patients. Methods Thirteen single-nucleotide polymorphisms (SNPs) at six RLS risk loci ( MEIS1, BTBD9, MAP2K5, PTPRD, TOX3, and an intergenic region on chromosome 2p14) were genotyped in 211 migraine patients with RLS and 781 migraine patients without RLS. Association analyses were performed for the overall cohort, as well as for the subgroups of patients who experienced migraines with and without aura and episodic migraines (EMs) vs. chronic migraines (CMs). In order to verify which genetic markers were potentially related to the incidence of RLS in migraine patients, multivariate regression analyses were also performed. Results Among the six tested loci, only MEIS1 was significantly associated with RLS. The most significant SNP of MEIS1, rs2300478, increased the risk of RLS by 1.42-fold in the overall cohort ( p = 0.0047). In the subgroup analyses, MEIS1 augmented the risk of RLS only in the patients who experienced EMs (odds ratio (OR) = 1.99, p = 0.0004) and not those experiencing CMs. Multivariate regression analyses further showed that rs2300478 in MEIS1 (OR = 1.39, p = 0.018), a CM diagnosis (OR = 1.52, p = 0.022), and depression (OR = 1.86, p = 0.005) were independent predictors of RLS in migraine. Conclusions MEIS1 variants were associated with an increased risk of RLS in migraine patients. It is possible that an imbalance in iron homeostasis and the dopaminergic system may represent a link between RLS incidence and migraines.

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Causal associations of obesity with chronic kidney disease and arterial stiffness: a Mendelian randomization study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab633 ◽

2021 ◽

Author(s):

Chaojie Ye ◽

Lijie Kong ◽

Zhiyun Zhao ◽

Mian Li ◽

Shuangyuan Wang ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Standard Deviation ◽

Kidney Disease ◽

Single Nucleotide Polymorphisms ◽

Arterial Stiffness ◽

Genetic Risk ◽

Mendelian Randomization ◽

Genetic Risk Score ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

Abstract Purpose Observational studies have associated obesity with chronic kidney disease (CKD) and arterial stiffness, but the causality remains unclear. We aimed to investigate the causality of obesity with CKD and arterial stiffness using Mendelian randomization (MR) analysis. Methods We genotyped 14 body mass index (BMI)-associated variants validated in East Asians in 11384 Chinese adults. A genetic risk score based on the 14 variants and the 14 individual single nucleotide polymorphisms were respectively used as instrumental variables (IVs). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m 2. Arterial stiffness was defined as brachial-ankle pulse wave velocity >1550 cm/s. Results Using the genetic risk score as the IV, we demonstrated causal relations of each 1-standard deviation increment in BMI with CKD (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.11-5.00) and arterial stiffness (OR: 1.71; 95% CI: 1.22-2.39). Using the 14 single nucleotide polymorphisms individually as IVs, each 1-standard deviation increment in BMI casually associated with CKD (OR: 2.58; 95% CI: 1.39-4.79) and arterial stiffness (OR: 1.87; 95% CI: 1.24-2.81) in the inverse-variance weighted analysis, and MR-Egger regression revealed no evidence of horizontal pleiotropy (Both P for intercept≥0.34). The causality between obesity and CKD was validated in two-sample MR analysis among Europeans (681275 of Genetic Investigation of ANthropometric Traits and 133413 of CKD Genetics). Conclusions This study provided novel insights into causality of obesity with CKD and arterial stiffness, highlighting the importance of weight management for primary prevention and control of subclinical vascular diseases.

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