ApoB Gene Polymorphisms Research Articles

Haplotype analysis and linkage disequilibrium of ApoB gene polymorphisms and its relationship with hyperlipidemia in patients with acne vulgaris.

Acne vulgaris (AV) is a chronic, multifactorial inflammatory disease of the pilosebaceous unit brought on by hormonal imbalance, excessive sebum production, follicular hyperkeratinization, inflammation and Cutibacterium acne. Acne patients are characterized by alteration of the lipid profile. Apolipoprotein B gene (ApoB) plays an essential role in lipoprotein biosynthesis and multiple single-nucleotide polymorphisms (SNPs) in ApoB are associated with dyslipidemia. The aim of this study was to estimate the alteration of lipid profiles in AV, determine the genetic association with lipid profile alteration by studying the ApoB gene polymorphisms, and to identify the exact haplotypes associated with acne and lipid profile alteration. In a case-control study consisting of 63 non-obese acne patients and 43 healthy controls, all participants underwent biochemical, anthropological assessments, and genetic analysis for ApoB polymorphisms. Our results indicate that serum ApoB and the lipid profile were higher in acne patients compared with healthy subject. The most common haplotypes in acne patients were rs562338 A/rs17240441 I/c.12669 A/rs1042034 G, whereas the most common haplotypes in healthy subjects were rs562338 G/rs17240441 D/c.12669 A/rs1042034 G. Patients with mild acne had higher serum ApoB levels p= 0.005. Also, the low-density lipoprotein cholesterol (LDL-C) level was higher in mild acne compared with other acne groups, with a highly significant variation of p≤0.001. We found a significant variation between the acne group and healthy controls in serum ApoB, triglycerides, total cholesterol and LDL-C. The most common haplotypes in acne patients are rs562338 A/, rs17240441 I/, c.12669 A/ and rs1042034 G, and there is a linkage disequilibrium between the four selected SNPs.

Effect of APOB gene polymorphisms on body mass index, blood pressure, and total cholesterol levels: A cross-sectional study in Mexican population.

APOB gene polymorphisms are considered risk factors for the development of dyslipidemia, hypertension, and cardiovascular disease (CVD) in several populations. In Mexico, these pathologies are frequent and studies regarding this gene are scarce. The aim of this cross-sectional study was to determined genotype, allele, and haplotype frequencies of APOB polymorphisms and performed analyses of association among the biochemical, hemodynamic, anthropometrical, and genetic variables. Blood samples were taken from 361 subjects from unselected Mexican population for biochemical analysis and for deoxyribonucleic acid extraction; besides blood pressure and body mass index (BMI) were measured. APOB polymorphisms rs934197, rs533617, rs693, and rs1042031 were genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism; whereas, rs17240441 and c.66_67insCTGCTG were genotyped by PCR followed by electrophoresis. Genotype and allele frequencies were obtained by simple counting and deviations from Hardy-Weinberg equilibrium (HWE) were calculated by chi-square test. The effect of the polymorphisms on the quantitative variables was determined using analysis of variance, Student’s t test, Pearson’s and Spearman’s correlations and multiple linear regression models. All the polymorphisms were within HWE. Frequencies of mutated alleles were highly heterogeneous: rs934197-T 33.6%, rs17240441-D 39.3%, c.66_67insCTGCTG-I 3.9%, rs533617-G 0.9%, rs693-T 40.5%, and rs1042031-G 17.3%. Chronic degenerative diseases were frequent in the studied population: overweight-obesity 55.1%, dyslipidemia 45.8%, and hypertension 23.5%. The association analyses showed that despite adjustments for age and sex the mutated alleles rs934197-T, rs1042031G, c.66_67-insCTGCTG-I, and rs533617-G, were related to lower values of BMI, total cholesterol (TC), systolic blood pressure, and diastolic blood pressure, respectively. All polymorphisms analyzed except rs533517 and c.66_67insCTGCTG showed high frequencies of the mutated allele, making them useful for association studies. Our results revealed that, APOB gene polymorphisms could be contributing to the development of several chronic diseases, such as essential hypertension, dyslipidemias, obesity, among others. However, specific studies with each pathology are needed to know the possible implications of the polymorphisms.

Association of XbaI polymorphism of ApoB gene with lipid profile, risk factors and dietary pattern in coronary artery disease Egyptian rural and urban patients

Background: Coronary artery disease (CAD) is a complex disorder. It is thought to be a result of gene-gene and gene-environment interactions. It was reported that XbaI polymorphism of ApoB gene is associated with CAD. However, the results were conflicting and risk factors were not fully studied in the previous studies. Aim: It was to estimate the association of XbaI polymorphism of ApoB gene with lipid profile, risk factors and dietary pattern in CAD Egyptian population. Subjects and Methods: This study was conducted on 400 Egyptians (200 healthy subjects; 100 Rural and 100 Urban controls and 200 CAD patients; 100 Rural and 100 Urban patients). CAD patients were diagnosed on the bases of clinical and angiographic assessment. Polymerase chain reaction – Restriction Fragment Length Polymorphism (PCR-RFLP) was used to genotype ApoB XbaI polymorphism of ApoB gene. Results: The ApoB XbaI X+X+ genotype frequency was higher in urban control versus urban CAD subgroups. Multivariate analysis revealed that male gender, hypertension, smoking, increased body mass index (BMI), high serum total cholesterol (TC), low serum high density lipoprotein cholesterol (HDL-C) and high score of unhealthy diet were associated with CAD increased risk, while high score of healthy diet was protective.

PB2330: CORONARY ARTERY DISEASE (CAD) AND XBAI GENE POLYMORPHISM (RS693) IN EGYPTIAN PATIENTS

Background: Coronary artery disease (CAD) is a multifactorial disease leading to coronary arteries occlusion in the form of ischemic heart events. Although cardiovascular diseases (CVD) mortality have been decreasing in the developed countries along the last decade, it is still rising in the developing countries(Popkin, Adair, & Ng, 2012).Egypt has the largest population in middle east and north Africa with significant high CAD mortality rate. In 2014, about 23.14% of all deaths in Egypt were caused by CAD. This made Egypt ranked 23rd in the world(El-Moselhy et al., 2018; Ralapanawa & Sivakanesan, 2021). Aims: To determine the relationship between the presence of XbaI gene polymorphisms and coronary arteries occlusion in Egyptian CAD patients. Methods: This is a case-control study conducted on 200 CAD Subjects (153 men and 47 women) with a median age of 57.5 ± 8.73 years old and 200 control subjects (127 men and 73 women) with a median age of 56.06 ± 6.56 years. The patients were selected from Mansoura University Hospitals clinics. DNA was extracted from leukocytes using spin column (Qiagen Co. Germany). DNA sequence containing Apo B gene was amplified by PCR using set of primers (Metabion, Germany). The amplified sequence was digested at 37 C with 20 U of XbaI restricton enzyme. Digests were run on 2 % agarose gel at 50 V in 1X Tris–borate- EDTA (TBE) buffer. It resulted in fragments of 741 and 201 bp in the presence of the restriction site (X+ allele). In the absence of the XbaI cutting site, the only produced band on the agarose gel was the 942 bp sequence. Results: X+X- genotype of XbaI (rs693) polymorphism was the most common among patients (48.5%) and controls (44%). There were no significant difference regarding genotypes and alleles of both studied polymorphisms between CAD group and controls. However, X+X+ genotype of XbaI (rs693) polymorphism had non-significant increase (approaching significance) in controls compared to CAD (P=0.056). No significant differences were found between multivessel CAD patients versus single vessel CAD patients regarding genotypes and alleles of XbaI (rs693), however non-significant higher frequency of X+X+ genotype were found in single vessel vs. multi-vessel CAD patients (12.8 vs. 8.4%; OR=0.645). Image:Summary/Conclusion: XbaI ApoB gene polymorphisms showed no significant difference between CAD and control groups in the studied Egyptian patients. There is also no significant difference between uni-vessel and multi-vessel patients groups.

Macronutrient intake modulates impact of EcoRI polymorphism of ApoB gene on lipid profile and inflammatory markers in patients with type 2 diabetes

We sought to examine whether dietary intakes may affect the relationship between ApoB EcoRI and lipid profile, as well as serum inflammatory markers, in patients with type 2 diabetes (T2DM). This current study consisted of 648 diabetic patients. Dietary intake was calculated by a food frequency questionnaire. Biochemical markers (high-density lipoprotein (HDL), total cholesterol (TC), LDL, TG, CRP, IL-18, PGF2α) were measured based on standard protocols. Genotyping of the Apo-B polymorphisms (rs1042031) was conducted by the PCR–RFLP method. The gene-diet interactions were evaluated using GLMs. In comparison to GG homozygotes, A-allele carriers with above the median -CHO intake (≥ 54 percent of total energy) had considerably greater TC and PGF2a concentrations. Furthermore, as compared to GG homozygotes, A-allele carriers with above the median protein intake (≥ 14 percent of total energy) had higher serum levels of TG (P = 0.001), CRP (P = 0.02), TG/HDL (P = 0.005), and LDL/HDL (P = 0.04) ratios. Moreover, A-allele carriers with above the median total fat intake (≥ 35 percent of total calories) had significantly higher TC level (P = 0.04) and LDL/HDL (P = 0.04) ratios compared to GG homozygotes. Furthermore, when compared to GG homozygotes, A-allele carriers who consumed above the median cholesterol (> 196 mg) had greater TG (P = 0.04), TG/HDL (P = 0.01) ratio, and IL-18 (P = 0.02). Furthermore, diabetic patients with the GA, AA genotype who consume above the median cholesterol had lower ghrelin levels (P = 0.01). In terms of LDL/HDL ratio, ApoB EcoRI and dietary intakes of specific fatty acids (≥ 9 percent for SFA and ≥ 12 percent for MUFA) had significant interaction. LDL/HDL ratio is greater in A-allele carriers with above the median SFA intake (P = 0.04), also when they consumed above the median MUFA this association was inverse (P = 0.04). Our study showed that plasma lipid levels in participants carrying the (AA or AG) genotype were found to be more responsive to increasing the percentage of energy derived from dietary fat, CHO, protein, SFA, and cholesterol consumption. Therefore, patients with a higher genetic susceptibility (AA or AG) seemed to have greater metabolic markers with a higher percentage of macronutrient consumption. Also, ApoB EcoRI correlations with metabolic markers might be attenuated with above the median MUFA consumption.

Gender Differences in 10-Year Mortality in Patients with Coronary Artery Disease with Elevated Lipoprotein(a): In Search of Invisible Guardian Angel

The objective of our study was to examine the contribution of elevated Lp(a) to 10-year mortality in 140 CAD patients, depending on gender, baseline lipid levels, ApoA-I, ApoB, and the ApoA1, ApoE, and ApoB gene polymorphisms. Methods and Results: The study included 140 patients (75 men and 65 women) of the Uzbek population, hospitalized with diagnosis “CAD, unstable angina (IIB class, E. Braunwald et al., 1989)” (main group) in the period between January 2009 and February 2011. The endpoints at 10-year follow-up were death from cardiovascular causes (fatal myocardial infarction and sudden cardiac death). In the studied cohort of CAD patients, Lp(a) distribution was skewed to the right, the median was 16.9mg/dL, and the mean was 34.3mg/dL. At the same time, Lp(a) value greater than the 75th percentile was >41mg/dL. In this regard, we compared the baseline values in 2 groups of patients: Group 1 (Lp(a)<41mg/dL) and Group 2 (Lp(a)>41mg/dL). The 10-year cardiovascular mortality rate was higher significantly in Group 2 (RR =3.67; 95% CI: 1.67-8.11; P=0.0013). Cardiovascular mortality was significantly higher (P<0.001) in men of Group 2 than in men of Group 1 (RR=5.31; 95% CI: 2.03-13.88; P<0.001), while in women, the 10-year mortality in the compared groups did not differ significantly. Cardiovascular mortality was lower in patients with ApoA-1≥140mg/dL, the majority of whom were women. Conclusion: In the absence of targeted Lp(a) therapy, long exposure to a level of Lp(a) of >41mg/dL is a factor that increases 10-year mortality in CAD patients. Highlights • 10-year cardiovascular mortality was higher in CAD patients with Lp(a)>41mg/dL. • However, the increase in mortality due to high Lp(a) was statistically significant in men than in women. • The ApoA-I level was higher in women than in men. • Cardiovascular mortality was lower in patients with ApoA-I≥140mg/dL, most of whom were women.

ApoB gene polymorphism (rs676210) and its pharmacogenetics impact on atorvastatin response among Iraqi population with coronary artery disease

BackgroundDrug response is below genetic influence, proven by the genetic variants. Pharmacogenetics trials are performed in many diseases, including coronary artery disease. This study was designed to determine the genetic polymorphism (rs676210) Pro2739leu G > A in the lipid metabolism-related gene (ApoB gene) and its pharmacogenetic role in the response to atorvastatin drug in a sample of Iraqi population with coronary artery disease (CAD). ResultsSignificant differences of genotype distribution in CAD patients and controls were observed in ApoB+ 8216 in Iraqi population from Hardy Weinberg Analysis. It also found that dramatic difference of low-density lipoprotein (LDL-C) level in response to 40 mg/day of atorvastatin therapy, the minor allele (A) observed a greater LDL-C lowering than the wild type allele (G). In ANOVA analysis, the result showed that the rs676210, Pro2739Leu, in ApoB gene increased non significantly, but gradually in plasma level of total cholesterol (TC), triglyceride (TG), very low-density lipoprotein (VLDL), and oxidize low-density lipoprotein (oxLDL) in the order of genotype AA, GA, and GG in response to 40 mg atorvastatin. ConclusionWe found the results highlighted the function of the rs676210, Pro2739Leu, in the ApoB gene in CAD etiology, and the findings support this variant’s impact in predicting the response of (LDL-C) to 40 mg of atorvastatin therapy. ApoB gene polymorphism (rs676210, Pro2739Leu), specifically the AA genotype, may help to identify individuals who will profit from atorvastatin’s lowering effects.

APOB gene polymorphisms may affect the risk of minor or minimal bleeding complications in patients on warfarin maintaining therapeutic INR.

The purpose of this study was to investigate influence of gene polymorphisms of APOB and APOE on risk of bleeding complications at therapeutic INR, during warfarin treatment in Korean patients with mechanical cardiac valves. The study included 142 patients from the EwhA-Severance Treatment Group (EAST) of Warfarin. A total of 12 SNPs was investigated. Five SNPs of APOB (c.13013G>A, c.1853C>T, c.1594C>T, c.293C>T, and c.7545C>T) and five SNPs of APOE (g.4798T>G, g.6406G>A, g.10413T>C, c.388T>C, and c.526C>T) were selected. In addition to selected SNPs, VKORC1 g.6399C>T, and CYP2C9 c.1075A>C, which were known to have significant effects on warfarin stable doses, were also included in the study. Two SNPs of APOB (c.293C>T and c.1853C>T) were associated with bleeding complications. T allele carriers of c.293C>T had 8.6 times (95% CI 2.9-25.5, p < 0.001) increased risk of bleeding, and attributable risk was 88.3%. C allele carriers of c.1853C>T had 6.4 times (95% CI 2.3-17.9, p < 0.001) increased risk of bleeding after adjusting for covariates (attributable risk of 84.3%). AUROC values of models that included c.1853C>T and c.293C>T were 0.771 and 0.802, respectively. Among demographic characteristics, age was the only significant factor. This study revealed that APOB was associated with bleeding complications in patients with warfarin treatment after mechanical cardiac valves.

Clinical Implication of ApoB (12669G/A) Gene Polymorphism and Risk of Cardio Vascular Disease in Indian Population

Background: Cardiovascular disease is rising day by day due to having high fat diet and due to genetic alterations. Materials & Methods: Study included 70 CVD patients and their peripheral blood samples were collected for genotyping by venipuncture under aseptic condition in EDTA vials (2ml) as well as in serum vials (3ml) for biochemical parameters. Genomic DNA extraction was done by phenol chloroform method from blood samples collected in EDTA vials from cases as well as controls for genotype study. Results: The difference of genotype between cases and controls was found to be significant (p=0.0003). Study observed that high percentage of GA 29 (41.4%) and AA 8 (11.4%) genotype was found in patients compared to controls GA 10 (20%) and AA 0 (0%) while lower GG 33 (47.2%) genotype in patients compared to control GG 40 (80%) genotype. Compared to the GG genotype, the OR 3.51 (1.49-8.25) and 20.55 (1.14-369.6) for the heterozygous GA and homozygous AA genotypes were estimated, suggesting a possible dominant effect of Apo B polymorphism on CVD risk. In smokers, compared to the GG genotype, the OR 2.19 (0.69-6.88) and 1.71 (0.29-9.87) for the heterozygous GA and homozygous AA genotypes. In alcoholism, compared to the GG genotype, the OR 2.66 (0.93-7.57) and 8.4 (0.92-76.19) for the heterozygous GA and homozygous AA genotypes. Patients with mutant homozygous AA, heterozygous GA genotypes showed 123.3+14.34 (mg/dl) and 76.92+24.09 Apo B level in CVD patients compared to wild type GG homozygous genotypes were 70.82+17.12. Conclusion: It was observed that Apo B gene polymorphism and smoking behaviour found to be associated with increased risk of CVD in Indian population.

Apolipoprotein B and angiotensin-converting enzyme polymorphisms and aerobic interval training: randomized controlled trial in coronary artery disease patients.

Physical training has been strongly recommended as a non-pharmacological treatment for coronary artery disease (CAD). Genetic polymorphisms have been studied to understand the biological variability in response to exercise among individuals. This study aimed to verify the possible influence of apolipoprotein B (ApoB: rs1042031 and rs693) and angiotensin-converting enzyme (ACE-ID: rs1799752) genotypes on the lipid profile and functional aerobic capacity, respectively, after an aerobic interval training (AIT) program in patients with CAD and/or cardiovascular risk factors. Sixty-six men were randomized and assigned to trained group (n=32) or control group (n=34). Cardiopulmonary exercise test was performed to determine the ventilatory anaerobic threshold (VAT) from cardiorespiratory variables. The AIT program, at an intensity equivalent to %VAT (70–110%), was conducted three times a week for 16 weeks. ApoB gene polymorphisms (−12669C>T (rs1042031) and −7673G>A (rs693)) were identified by real-time polymerase chain reaction (PCR). I/D polymorphism in the ACE gene (rs1799752) was identified through PCR and fragment size analysis. After 16 weeks, low-density lipoprotein (LDL) levels increased in the trained and control groups with the GA+AA genotype (−7673G>A) of the ApoB gene. Trained groups with ACE-II and ACE-ID genotypes presented an increase in oxygen consumption (VO2VAT) and power output after the AIT program. The presence of the ACE I-allele was associated with increased aerobic functional capacity after the AIT program. Increased LDL levels were observed over time in patients with the −7673G>A polymorphism of the ApoB gene. Trial Registration Information: ClinicalTrials.gov: NCT02313831

Variants in the APOB gene was associated with Ischemic Stroke susceptibility in Chinese Han male population.

BackgroundStroke is an extremely complicated disease caused by multiple factors. Epidemiological studies have shown that genetic factors contribute to the pathogenesis of stroke. There is still little research on the effect of ApoB gene on stroke in Chinese Han population. The purpose of our research was to explore the effect of ApoB gene polymorphism on the genetic susceptibility to Ischemic Stroke in Chinese Han male population.Materials and methods7 polymorphisms in ApoB gene were selected and genotyped using Sequenom MassARRAY in 325 ischemic stroke male patients and 399 healthy male controls in Chinese Han population. The association between ApoB gene and genetic susceptibility to Ischemic Stroke was performed by the χ2 test, genetic model analysis and haplotype analysis.ResultsIn the allele model, ApoB rs1042034 “T” allele and rs673548 “G” allele increased the risk of the Ischemic Stroke (rs1042034: OR=1.29, 95%CI: 1.02-1.63, p=0.030; rs673548: OR=1.28, 95%CI: 1.02-1.62, p=0.034). Logistic regression analysis found that ApoB rs1042034 and rs673548 increased the risk of Ischemic Stroke in the log-additive model, the odds of having Ischemic Stroke would be 1.28-fold and 1.27-fold with the variant allele, respectively. We also found that the risk of individuals carrying the ApoB rs693 “AA-AG” genotype had Ischemic Stroke risk of 1.52-fold of carrying “GG” genotype in the dominant model. The haplotype analysis shown that “TAG” haplotype raised the risk of Ischemic Stroke (OR=1.52, 95%CI: 1.02-2.27, p=0.0042).ConclusionThe polymorphisms of the ApoB gene may affect Ischemic Stroke occurrence.

The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis

Background and aimsGenetic studies have been reported on the association between APOA5, APOB, APOC3 and ABCA1 gene polymorphisms and ischemic stroke, but results remain controversial. Hence, this meta-analysis aimed to infer the causal relationships of APOA5 (rs662799, rs3135506), APOB (rs693, rs1042031, rs1801701), APOC3 (rs4520, rs5128, rs2854116, rs2854117) and ABCA1 rs2230806 with ischemic stroke risk. MethodsA systematic review was performed for all the articles retrieved from multiple databases, up until March 2017. Data were extracted from all eligible studies, and meta-analysis was carried out using RevMan 5.3 and R package 3.2.1. The strength of association between each studied polymorphism and ischemic stroke risk was measured as odds ratios (ORs) and 95% confidence intervals (CIs), under fixed- and random-effect models. ResultsA total of 79 studies reporting on the association between the studied polymorphisms and ischemic stroke risk were identified. The pooled data indicated that all genetic models of APOA5 rs662799 (ORs = 1.23–1.43), allelic and over-dominant models of APOA5 rs3135506 (ORs = 1.77–1.97), APOB rs1801701 (ORs = 1.72–2.13) and APOB rs1042031 (ORs = 1.66–1.88) as well as dominant model of ABCA1 rs2230806 (OR = 1.31) were significantly associated with higher risk of ischemic stroke. However, no significant associations were observed between ischemic stroke and the other five polymorphisms, namely ApoB (rs693) and APOC3 (rs4520, rs5128, rs2854116 and rs2854117), under any genetic model. ConclusionsThe present meta-analysis confirmed a significant association of APOA5 rs662799 CC, APOA5 rs3135506 CG, APOB rs1801701 GA, APOB rs1042031 GA and ABCA1 rs2230806 GG with increased risk of ischemic stroke.

Interaction between APOB gene polymorphism and risk factors in coronary heart disease patients without lipid-lowering treatment

Objective: To investigate the association between APOB gene R532W polymorphism and the risk of coronary heart disease (CHD) in patients without lipid-lowering treatment and to analyze the interactions between the variation of R532W and different risk factors of CHD. Methods: CHD and non-CHD were diagnosed according to coronary artery angiography (CAG) and/or coronary computed tomography angiogram (CTA) results, as well as clinical features. Blood samples from 771 CHD patients and 772 age- and sex-matched non-CHD controls, who never accepted any lipid-lowering treatments, were collected. R532W was genotyped by HumanExome BeadChip at BGI and strict quality control was made. Firstly, the association between R532W polymorphism and the risk of CHD in 3 genetic models (GA+ AA vs.GG, AA vs. GG+ GA, AA vs. GA vs. GG) after adjusting confounding factors was explored. Then, the interactions between the variation of this loci and risk factors related to CHD were investigated. Results: (1) Total cholesterol (TC) levels were significantly lower in AA genotype than in GA genotype in the total cohort and non-CHD controls, but was similar among the 3 genotypes in CHD patients. (2) R532W GG, GA and AA distribution was 80.7%, 18.2% and 1.2% in CHD patients, and 74.6%, 23.8% and 1.6% in non-CHD controls (P<0.05). (3) R532 polymorphism was related to the incidence of CHD in the dominant model, and A-allele carriers were related to about 35% reduced risk of CHD (OR=0.653, 95% CI 0.502-0.849, P=0.001) after adjusting for confounding factors. (4) R532W polymorphism had positive interactions with hypertension (1.452) and smoke (1.077), while negative interaction with diabetes (0.553) in the occurrence of CHD. Conclusions: APOB gene R532W polymorphism is related to TC levels in Chinese north Han population. A-allele carries of R532W loci is linked with reduced risk of CHD in the absence of lipid-lowering treatment. R532W polymorphism has a positive additive interaction with hypertension and smoke, while a negative additive interaction with diabetes mellitus in the occurrence of CHD.

Role of ApoB-516C/T promoter gene polymorphism in the risk of Hepatitis C virus infection in Egyptian patients and in gender susceptibility.

At least 1 in 10 of the Egyptian population aged 15-59 is burdened with hepatitis C virus (HCV) infection, stamping Egypt the highest country harboring HCV worldwide. Considerable evidence supported the involvement of host genetic factors in the pathogenesis of HCV and the possibility of implementation in target therapies. ApoB gene polymorphisms are postulated to affect the susceptibility of HCV infection. Hence, we aimed to evaluate the relationship between ApoB-516C/T promoter gene polymorphism and HCV infection in a cohort of Egyptian patients and to explore whether higher levels of low-density lipoprotein (LDL) might compete with lipoviral particles (LVP) in the binding to LDL receptor (LDLR), thus escaping infection. Ninety-seven HCV patients and 96 matched controls were enrolled in this study. We genotyped ApoB-516C/T using PCR-RFLP method. ApoB concentrations were measured by immunoturbidimetric assay. The genotype and the allele frequencies of ApoB-516C/T promoter gene polymorphism in cases were statistically insignificant compared with healthy individuals (P = 0.109, 0.125, respectively). Sex stratification showed significantly lower counts of C/T genotype in female patients compared with female controls (P = 0.011, OR = 0.132, 95% CI = 0.026-0.657). Significantly higher levels of LDL and ApoB were detected in the control group (P < 0.001). This study shows that the ApoB-516C/T promoter gene polymorphism has no impact on the risk of HCV infection. However, the C/T genotype may be a protective factor for our female cohort. Further studies with larger samples are needed to verify this genetic gender diversity. Additionally, high levels of LDL and ApoB might prevent HCV infection.

Association between Insertion/Deletion Polymorphism of ApoB Gene with Dyslipidemia and Obesity Risk in Patients with Type 2 Diabetes

Association between Insertion/Deletion Polymorphism of ApoB Gene with Dyslipidemia and Obesity Risk in Patients with Type 2 Diabetes

Dietary ω-3 polyunsaturated fatty acid intake modulates impact of Insertion/Deletion polymorphism of ApoB gene on obesity risk in type 2 diabetic patients

ObjectivesThe goal of the study described here was to determine whether dietary ω-3 polyunsaturated fatty acid (PUFA) intake modulates the association between ApoB Ins/Del polymorphism and obesity in type 2 diabetic patients. MethodsIn this cross-sectional study, 700 patients with type 2 diabetes were recruited in Tehran. Weight and waist circumference (WC) were measured, and body mass index (BMI) was calculated. Dietary intake was assessed using a validated semiquantitative food frequency questionnaire. ApoB genotyping was performed with 8% polyacrylamide gel electrophoresis. ResultsWe observed a significant interaction between Ins/Del genotype and dietary ω-3 PUFA intake with respect to BMI, WC, and obesity risk in both unadjusted (P = 0.007, P = 0.001, and P = 0.021, respectively) and adjusted (P = 0.007, P = 0.04, and P = 0.002, respectively) samples. Thus, the carriers of the Del allele were only associated with lower BMI (P = 0.01) and WC (P = 0.002) among individuals with high ω-3 PUFA intake (≥0.6% of energy), but not in those with low ω-3 PUFA intake (<0.6%). Also, when dietary ω-3 PUFA was <0.6%, general obesity risk in carriers of the Del allele was about 1.6 times higher than that of Ins/Ins homozygotes (odds ratio = 1.59, 95% confidence interval: 1.05–2.52, P = 0.039). But with high ω-3 PUFA intake (≥0.6%), the risk was 0.46 times lower (odds ratio = 0.46, 95% confidence interval: 0.25–0.79, P = 0.003). Moreover, a similar interaction was observed in central obesity only in men after adjustment for confounder variables (P = 0.041). ConclusionsThese findings support the hypothesis that a diet high in ω-3 PUFA (≥0.6%) can decrease the obesity risk in carriers of the Del allele of ApoB gene.

The APOB gene polymorphism in the pathogenesis of gallstone disease in pre- and postmenopausal women.

Aim of the studyThe decrease in estrogen levels in the postmenopausal period changes the lipid profile by the expression of hepatic genes related to metabolism of cholesterol and bile acid synthesis that could be important in the pathogenesis of cholelithiasis. The aim of the study was to determine the APOB gene 7673C>T and 12669G>A polymorphisms in the pathogenesis of gallstones and analysis of the composition of gallstones in pre- and postmenopausal women.Material and methodsThe study group consisted of 94 women qualified to the laparoscopic cholecystectomy while the control group consisted of 81 women in whom gallstones and other changes in the bile ducts were excluded. Gallstones composition analysis was performed using commercially available assays. The prevalence of the APOB gene polymorphisms was determined using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).ResultsWhen assessing the composition of gallstones in pre- and postmenopausal women, we observed differences in the studied parameters. Analysis of genetic variants of APOB gene 7673C>T and 12669G>A polymorphisms showed no significant statistical differences between studied groups and controls.ConclusionsAnalysis of 7673C>T and 12669G>A polymorphisms showed no relationship between specific genetic variants and the risk of gallstones in pre- and postmenopausal women, pointing to the fact that the investigated polymorphisms are not relevant as prognostic factors in gallstone disease in the Caucasian population. Because of the possible contribution of a variety of factors in gallstones pathogenesis the studies are required to take account of additional environmental factors, what may indicate different occurrence between investigated polymorphisms, gallstone disease development and gallstones composition in Caucasians.

Relationship of the APOA5/A4/C3/A1 gene cluster and APOB gene polymorphisms with dyslipidemia.

We determined the alleles of ten single nucleotide poly-morphisms (SNPs) in the APOA5/A4/C3/A1 gene cluster and in APOB in Han Chinese from Xinjiang Shihezi, China using MALDI-TOF mass spectrometry, and explored the correlation between these SNPs and dyslipidemia through a case-control study design with 250 pa-tients and 250 normal controls. All SNPs except for APOA5 rs2072560 conformed to Hardy-Weinberg equilibrium (all P > 0.05). APOA5 rs651821, APOA4 rs5104, APOC3 rs734104, and APOC3 rs5128 geno-type and allele frequencies were significantly different between groups (all P < 0.01). For rs651821, the risks of dyslipidemia for the CC or CC+CT genotypes were 9.917 or 1.859 times that of TT, and the risk of the C vs T allele was 2.027. For rs5104, the AG, GG, or AG+GG risks were 1.797, 1.861, and 1.809 times AA, and the G vs A risk was 1.427. For rs734104, the CT, CC, or CC+CT risks were 1.851, 2.570, and 1.958 times TT, and the C vs T risk was 1.610. For rs5128, the GC or CC+GC risks were 1.738 or 1.749 times GG, and the C vs G risk was 1.477. Compared with the wild-type haplotype TATG, the risks of dyslipidemia with CGCC, TGCC, or CATG haplotypes (odds ratios = 2.434, 1.503, and 2.740, respectively) were significantly higher. Our results suggested that these four SNPs were significantly associated with dyslipidemia in Xinjiang Shihezi Han Chinese, and might serve as risk factors for dyslipidemia. Individuals carrying the CGCC, TGCC, or CATG haplotypes were prone to dyslipidemia.

Study on Association of APOB Gene Polymorphism with Glycation of Low Density Lipoproteinin Type 2 Diabetes

Objectives: Sustained hyperglycemia results in non-enzymatic glycation of Apo B or LDL particle which may affect its recognition and uptake. Increase in circulating LDL levels is a vital contributor for atherosclerosis. APOB gene (c.12669 G>A, p.GLN4154LYS) polymorphism is believed to be associated with coronary artery disease. We thus designed our study to evaluate association of APOB gene polymorphism with Apo B glycation in type 2 diabetic patients. Methods: A total of 45 non diabetic controls and 45 type 2 diabetic patients participated in this study. Following an overnight fast, venous blood was collected and analyzed for glycemic status, lipid profile and other biochemical parameters. Apo B was estimated using nephelometry, Glycated LDL was estimated by ELISA. PCR-RFLP was used to determine the DNA polymorphism in the APOB gene using EcoR1. Results: Polymorphic analysis of APOB gene in diabetic population showed 73.3% wild type (R+/R+), 20.0% heterozygous mutant (R+/R-) and 6.7% homozygous mutant (R-/R-). Significant associations of glycated LDL was observed with R-/R- and R+/ R- when compared with R+/R+. Significant association was not observed between Apo B levels and of genotypes. Conclusions: Presence of polymorphism may not affect the expression Apo B level but acts as an important contributor to LDL modification and increases its glycation. Since glycation of LDL reduces uptake of LDL by LDL receptors, it may increase the risk of atherosclerosis.

Relationship between the Apolipoprotein AI, B gene polymorphism and the risk of non-traumatic osteonecrosis.

BackgroundPrevious studies suggested that Apolipoprotein AI (ApoAI) and apolipoprotein B (ApoB) gene polymorphisms may result in lipid metabolism disorders. Genetic polymorphisms in these genes may be associated with the occurrence of osteonecrosis.MethodsWe designed a case-control study including 429 patients of osteonecrosis and 368 age- and sex-matched control subjects. Polymerase chain reaction was used to amplify the DNA fragments in promoter -75 G > A of ApoAI gene and EcoR I, Xba I and 3′-VNTR of ApoB gene in osteonecrosis patients and healthy controls. We utilized polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to genotype these four single nucleotide polymorphisms (SNPs).ResultsFor -75 G > A polymorphism of ApoAI, AA genotype frequency (0.501) was significantly higher in patients with osteonecrosis than that in control (0.462) subjects (P <0.001), GA genotype frequency (0.170) was significantly lower than that in the control (0.310) group (P <0.0001). In osteonecrosis patients, the odds ratio (OR) of A allele was 3.932 (95% CI: 3.0847 ~ 5.0123), which suggested that subjects carrying A allele of promoter region -75 G > A of ApoAI gene had higher susceptibility to osteonecrosis than G allele carriers. The genotype and allele frequency distributions showed no significant difference in EcoR I, Xba Iand 3′-VNTR loci of ApoB gene between the osteonecrosis group and control group.ConclusionOur study suggested that ApoAI gene -75G > A polymorphism may be associated with susceptibility to osteonecrosis in Chinese population. However, our results need further investigation with large sample size and various populations.