Contribution of the ACE (rs1799752) and CYP11B2 (rs1799998) Gene Polymorphisms to Atrial Fibrillation in the Tunisian Population

Background: This study investigated the association of angiotensin–converting enzyme (ACE I/D) and aldosterone synthase (CYP11B2-344C/T) gene polymorphisms in the renin–angiotensin–aldosterone system (RAAS) with atrial fibrillation (AF) in the Tunisian population. Materials and Methods: The study population included 120 patients with AF and 123 age-matched controls. Genotyping of the I/D polymorphism in the ACE gene and the -344C/T polymorphism in the CYP11B2 gene was performed by polymerase chain reaction (PCR) and PCR-RFLP methods, respectively. Results: The genotype distribution of the ACE I/D and CYP11B2-344C/T polymorphisms was significantly different between AF patients and control participants ( p < 0.01 and p < 0.006 respectively). In addition, ACE I/D increased the risk of AF significantly by 3.41-fold for the DD genotype (OR = 3.41; 95% CI [1.39–8.34]; p < 0.007), and after adjusting for confounding factors (age, diabetes, hypertension, and dyslipidemia), the risk was higher (OR = 5.71; 95% CI [1.48–21.98]; p < 0.01). Likewise, the CYP11B2-344C/T polymorphism increased the incidence of AF for the TT genotype (OR = 3.66; 95% CI [1.62–8.27]; p < 0.002) and the CT genotype (OR = 2.68; 95% CI [1.22–5.86]; p < 0.01). After adjusting for confounding factors (age, diabetes, hypertension and dyslipidemia), the risk remained higher for the TT genotype (OR = 3.58; 95% CI [1.08–11.77]; p < 0.03). Furthermore, the haplotype–based association of the ACE I/D and CYP11B2-344C/T polymorphisms showed that the D-T haplotype increased the risk for AF. Conclusion: Our study suggests a significant association of the ACE (I/D) and CYP11B2-344C/T polymorphisms with AF in the Tunisian population.

The effect of SOX4 gene 3′UTR polymorphisms on osteoporosis

Objective This study aimed to explore the correlation between the SRY-related high-mobility-group box gene 4 (SOX4) 3′ untranslated region (UTR) single nucleotide polymorphism (SNP) and osteoporosis susceptibility. Methods The study recruited 330 osteoporosis patients (the case group) and 330 non-osteoporosis patients (the control group) in Sichuan Chengdu First People’s Hospital and Zibo Central Hospital from August 2016 to August 2019. Sanger sequencing was used to analyze the genotypes of SOX4 gene rs79958549, rs139085828, and rs201335371 loci. Multi-factor dimensionality reduction (MDR) was used to analyze the interaction between the SOX4 gene rs79958549, rs139085828, and rs201335371 loci and the clinical characteristics of the subjects. Results The risk of osteoporosis in the carriers of A allele at SOX4 rs79958549 was 5.40 times that in the carriers of the G allele (95% CI 3.25–8.96, P < 0.01). The risk of osteoporosis in the carriers of the A allele at SOX4 rs139085828 was 1.68 times that in the carriers of the G allele (95% CI 1.45–1.85, P < 0.01). The risk of osteoporosis in the carriers of the T allele at SOX4 rs201335371 was 0.54 times that in the carriers of the C allele (95% CI 0.43–0.69, P < 0.01). The SOX4 gene rs79958549, rs139085828, and rs201335371 A-A-C haplotype (OR = 5.14, 95% CI 2.45–10.57, P < 0.01) were associated with increased risk of osteoporosis and G-G-T haplotype was significantly associated with decreased risk of osteoporosis (OR = 0.48, 95% CI 0.38–0.62, P < 0.01). The interaction among the factors of sex, smoking, drinking, rs79958549, rs201335371 was the best model for osteoporosis prediction, and the risk for osteoporosis in ‘high-risk combination’ was 2.74 times that of ‘low-risk combination’ (95% CI 1.01–7.43, P = 0.04). Multiple logistic regression analysis revealed that the risk factors for osteoporosis were BMD (OR = 5.85, 95% CI 2.88–8.94, P < 0.01), T score (OR = 8.54, 95% CI 5.66–10.49, P < 0.01), Z score (OR = 3.77, 95% CI 2.15–8.50, P < 0.01), rs79958549 SNP (OR = 6.92, 95% CI 3.58–8.93, P < 0.01), and rs139085828 SNP (OR = 2.36, 95% CI 1.85–4.27, P < 0.01). The protective factor for osteoporosis was rs201335371SNP (OR = 0.48, 95% CI 0.32–0.75, P < 0.01). Conclusion The SOX4 gene SNPs rs79958549, rs139085828, and rs201335371 loci were significantly associated with osteoporosis risk.

Interpretations of Probability

If you check the weather prediction on your phone, you might read that there is a 30 percent chance of rain at 4:00 in the afternoon. What does this mean? More precisely, what is the fraction 30/100 a measure of? Probability is a concept that is widespread both in everyday life and in science. Ordinary speakers of English utter and have some understanding of sentences such as “I will probably be late for the meeting,” or “it’s unlikely that Luxembourg will win the next World Cup.” Various sciences make explicit probabilistic claims: “the probability that a radium atom will decay in 1620 years is 0.5”; “the probability that a house mouse whose father is heterozygous for the t haplotype will inherit that trait is 0.9.” Other claims implicitly invoke probability: “the life expectancy of a child born in Japan today is 85.3 years.” Probability theory is also a major branch of mathematics, and it was given its modern formulation by Kolmogorov in 1933. Kolmogorov’s formalism presents a function P that satisfies a set of axioms: it is non-negative, normalized, and additive. These axioms entail a rich set of theorems concerning the behavior of P; together they make up the probability calculus. While the resulting theory is a formal theory in its own right, it is also natural to interpret P—to attach meanings, or truth conditions to claims involving it. ‘What is P?’, one may ask. This may be understood as a metaphysical question about what kinds of things are probabilities, or more generally as a question about what makes probability statements true or false. The various interpretations of probability attempt to answer this question, one way or another. This article surveys the literature on the interpretations of probability, due to mathematicians and especially philosophers. It divides the interpretations into two broad categories. Epistemological interpretations understand probability in terms of an agent’s beliefs, the strength of evidence in support of a statement, or other epistemological categories. Physical interpretations view probability as a feature of the world that would exist regardless of what evidence exists or what agents believe. This is a natural taxonomy, but others could be adopted, and its sub-categories are also somewhat pliable. The authors would like to thank Kim Border, Chris Bottomley, Kenny Easwaran, Hanti Lin, Charles Sebens, Glenn Shafer, Julia Staffel, Jeremy Strasser, and an anonymous referee for many helpful suggestions.

Effects of the dopamine transporter gene on striatal functional connectivity in youths with attention-deficit/hyperactivity disorder

Background The dopamine transporter gene (DAT1), striatal network dysfunction, and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine the effects of the DAT1 rs27048 (C)/rs429699 (T) haplotype on striatal functional connectivity and visual memory performance in youths with ADHD. Method After excluding those who had excessive head motion, a total of 96 drug-naïve youths with ADHD and 114 typically developing (TD) youths were assessed with the resting-state functional magnetic resonance imaging and the delayed matching to sample (DMS) task for visual memory. We examined the effects of ADHD, DAT1 CT haplotype, and the ADHD × CT haplotype interaction on the functional connectivity of five striatal seeds. We also correlated visual memory performance with the functional connectivity of striatal subregions, which showed significant diagnosis × genotype interactions. Results Compared with TD youths, ADHD youths showed significant hypoconnectivity of the left dorsal caudate (DC) with bilateral sensorimotor clusters. Significant diagnosis × genotype interactions were found in the connectivity between the left DC and the right sensorimotor cluster, and between the right DC and the left dorsolateral prefrontal/bilateral anterior cingulate clusters. Furthermore, the connectivity of the left DC showing significant diagnosis × genotype interactions was associated with DMS performance in youths with ADHD who carried the DAT1 CT haplotype. Conclusions A novel gene-brain-behavior association between the left DC functional connectivity and visual memory performance in ADHD youths with the DAT1 rs27048 (C)/rs429699 (T) haplotype suggests a differential effect of DAT1 genotype altering specific brain function causing neuropsychological dysfunction in ADHD.

Genetic Variants of CD40 Gene Are Associated with Coronary Artery Disease and Blood Lipid Levels

Objectives. The present study aimed to evaluate the effect ofCD40andCXCR4genes polymorphisms on CAD susceptibility and the blood lipid levels and history of cardiovascular risk factors in a Chinese Han population.Materials and Methods. A total of 583 unrelated patients with CAD and 540 controls were recruited. Two tag SNPs (rs4239702 and rs1535045) at theCD40locus and one tag SNP (rs2228014) at theCXCR4locus were genotyped using the SEQUENOM Mass-ARRAY system.Results. After adjusting the risk factors, the frequency of rs1535045-T allele was also higher in patients than controls. Haplotype analysis showed that the rs4239702(C)-rs1535045(T) haplotype was associated with CAD. People with rs4239702-TT genotype had higher blood lipid levels in case group while it was not in the control group. History of cardiovascular risk factors showed no association for the three SNPs in case group and control group.Conclusions. rs1535045 inCD40gene is likely to be associated with CAD in the Chinese Han population. rs4239702(C)-rs1535045(T) haplotype was associated with CAD. Only in CAD patients, the blood lipid level of patients with rs4239702-TT genotype was higher than other patients.CXCR4gene may not relate to CAD.

The Variants Within the COL5A1 Gene are Associated with Reduced Risk of Anterior Cruciate Ligament Injury in Skiers

The purpose of this study was to examine the association of the BstUI RFLP C/T (rs 12722) and DpnII RFLP C/T (rs 13946) COL5A1 polymorphisms, individually and as haplotypes, with anterior cruciate ligament ruptures in recreational skiers. Subjects were 138 male recreational skiers with surgically diagnosed primary anterior cruciate ligament ruptures. The control group consisted of 183 apparently healthy male recreational skiers, who were without any self-reported history of ligament or tendon injury. DNA was extracted from buccal cells donated by the subjects and genotyping was carried out using real-time PCR. The genotype distributions for both polymorphisms met Hardy- Weinberg expectations in both groups. There were no significant differences in genotype distribution of allele frequencies of COL5A1 BstUI RFLP C/T and COL5A1 DpnII RFLP C/T polymorphisms between the ACL rupture and control groups. The T-T (BstUI RFLP T, DpnII RFLP T) haplotype was the most common (55.6%). The haplotype T-C was not present in any of the subjects. There was an underrepresentation tendency of the C-T haplotype in the study group compared to controls under recessive mode of inheritance. Higher frequency of the COL5A1 BstUI RFLP C/T and COL5A1DpnII RFLP C/T polymorphisms haplotype is associated with reduced risk of anterior cruciate ligament injury in a group of apparently healthy male recreational skiers.