Association of the CAG repeat polymorphism in mitochondrial polymerase gamma (POLG1) with male infertility: A case-control study in an Algerian population

Polymorphisms in the mitochondrial DNA polymerase gamma (POLG) have been speculated to be associated with male infertility. The main objective of our study was to assess the possible association of CAG repeat polymorphism in POLG1 gene and male infertility in Algerian population. Genomic DNA from 89 infertile men and 84 controls was extracted using salting-out method. CAG repeat polymorphism was analyzed by the automated direct sequencing protocol. Statistical analysis was performed by Epi-info® (v6.0) software. A significant association with male infertility was found for CAG repeat polymorphism in heterozygous genotypes (10/ ≠ 10 vs 10/10: OR = 2.00 [0.99 - 4.05], p = 0.03; “infertile vs control groups”; 10/≠10 vs 10/10: OR = 3.75 [1.20- 11.96], p=0.01 “oligoasthenoteratospermic group”). Also, the results showed a significant association between the morbid allele (≠10) and male infertility (2.07 [01.07 - 04.02], p = 0.01). Our results showed that POLG1 CAG repeat polymorphism might be a risk factor for male infertility in Algerian population. Investigations with larger sample sizes and representative population-based cases and matched controls are needed to validate our results. Les polymorphismes de l'ADN polymérase gamma mitochondriale (POLG) ont été supposés être associés à l'infertilité masculine. L'objectif principal de notre étude était d'évaluer l'association possible du polymorphisme de répétition CAG dans le gène POLG1 et l'infertilité masculine dans la population algérienne. L'ADN génomique de 89 hommes stériles et 84 témoins a été extrait en utilisant la méthode de salting-out. Le polymorphisme de répétition CAG a été analysé par le protocole de séquençage direct automatisé. L'analyse statistique a été réalisée par le logiciel Epi-info® (v6.0). Une association significative avec l'infertilité masculine a été trouvée pour le polymorphisme de répétition CAG dans les génotypes hétérozygotes (10 / ≠ 10 vs 10/10: OR = 2,00 [0,99 -4,05], p = 0,03; «infertiles vs groupes témoins»; 10 / ≠ 10 vs 10/10: OR = 3,75 [1,20-11,96], p = 0,01 «groupe oligoasthénotératospermique»). De plus, les résultats ont montré une association significative entre l'allèle morbide (≠ 10) et l'infertilité masculine (2,07 [1.07-4.02], p = 0.01). Nos résultats ont montré que le polymorphisme répété de POLG1 CAG pourrait être un facteur de risque d'infertilité masculine dans la population algérienne. Des enquêtes avec des échantillons de plus grande taille et des cas représentatifs basés sur la population et des témois appariés sont nécessaires pour valider nos résultats

Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial

Importance: It is unknown whether coronary revascularization, when added to optimal medical therapy, improves prognosis in patients with stable ischemic heart disease (SIHD) at increased risk of cardiovascular events owing to moderate or severe ischemia. Objective: To describe baseline characteristics of participants enrolled and randomized in the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial and to evaluate whether qualification by stress imaging or nonimaging exercise tolerance test (ETT) influenced risk profiles. Design, Setting, and Participants: The ISCHEMIA trial recruited patients with SIHD with moderate or severe ischemia on stress testing. Blinded coronary computed tomography angiography was performed in most participants and reviewed by a core laboratory to exclude left main stenosis of at least 50% or no obstructive coronary artery disease (CAD) (<50% for imaging stress test and <70% for ETT). The study included 341 enrolling sites (320 randomizing) in 38 countries and patients with SIHD and moderate or severe ischemia on stress testing. Data presented were extracted on December 17, 2018. Main Outcomes and Measures: Enrolled, excluded, and randomized participants' baseline characteristics. No clinical outcomes are reported. Results: A total of 8518 patients were enrolled, and 5179 were randomized. Common reasons for exclusion were core laboratory determination of insufficient ischemia, unprotected left main stenosis of at least 50%, or no stenosis that met study obstructive CAD criteria on study coronary computed tomography angiography. Randomized participants had a median age of 64 years, with 1168 women (22.6%), 1726 nonwhite participants (33.7%), 748 Hispanic participants (15.5%), 2122 with diabetes (41.0%), and 4643 with a history of angina (89.7%). Among the 3909 participants randomized after stress imaging, core laboratory assessment of ischemia severity (in 3901 participants) was severe in 1748 (44.8%), moderate in 1600 (41.0%), mild in 317 (8.1%) and none or uninterpretable in 236 (6.0%), Among the 1270 participants who were randomized after nonimaging ETT, core laboratory determination of ischemia severity (in 1266 participants) was severe (an eligibility criterion) in 1051 (83.0%), moderate in 101 (8.0%), mild in 34 (2.7%) and none or uninterpretable in 80 (6.3%). Among the 3912 of 5179 randomized participants who underwent coronary computed tomography angiography, 79.0% had multivessel CAD (n = 2679 of 3390) and 86.8% had left anterior descending (LAD) stenosis (n = 3190 of 3677) (proximal in 46.8% [n = 1749 of 3739]). Participants undergoing ETT had greater frequency of 3-vessel CAD, LAD, and proximal LAD stenosis than participants undergoing stress imaging. Conclusions and Relevance: The ISCHEMIA trial randomized an SIHD population with moderate or severe ischemia on stress testing, of whom most had multivessel CAD

Baseline characteristics and risk profiles of participants in the ISCHEMIA randomized clinical trial

Importance It is unknown whether coronary revascularization, when added to optimal medical therapy, improves prognosis in patients with stable ischemic heart disease (SIHD) at increased risk of cardiovascular events owing to moderate or severe ischemia. Objective To describe baseline characteristics of participants enrolled and randomized in the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial and to evaluate whether qualification by stress imaging or nonimaging exercise tolerance test (ETT) influenced risk profiles. Design, Setting, and Participants The ISCHEMIA trial recruited patients with SIHD with moderate or severe ischemia on stress testing. Blinded coronary computed tomography angiography was performed in most participants and reviewed by a core laboratory to exclude left main stenosis of at least 50% or no obstructive coronary artery disease (CAD) (<50% for imaging stress test and <70% for ETT). The study included 341 enrolling sites (320 randomizing) in 38 countries and patients with SIHD and moderate or severe ischemia on stress testing. Data presented were extracted on December 17, 2018. Main Outcomes and Measures Enrolled, excluded, and randomized participants’ baseline characteristics. No clinical outcomes are reported. Results A total of 8518 patients were enrolled, and 5179 were randomized. Common reasons for exclusion were core laboratory determination of insufficient ischemia, unprotected left main stenosis of at least 50%, or no stenosis that met study obstructive CAD criteria on study coronary computed tomography angiography. Randomized participants had a median age of 64 years, with 1168 women (22.6%), 1726 nonwhite participants (33.7%), 748 Hispanic participants (15.5%), 2122 with diabetes (41.0%), and 4643 with a history of angina (89.7%). Among the 3909 participants randomized after stress imaging, core laboratory assessment of ischemia severity (in 3901 participants) was severe in 1748 (44.8%), moderate in 1600 (41.0%), mild in 317 (8.1%) and none or uninterpretable in 236 (6.0%), Among the 1270 participants who were randomized after nonimaging ETT, core laboratory determination of ischemia severity (in 1266 participants) was severe (an eligibility criterion) in 1051 (83.0%), moderate in 101 (8.0%), mild in 34 (2.7%) and none or uninterpretable in 80 (6.3%). Among the 3912 of 5179 randomized participants who underwent coronary computed tomography angiography, 79.0% had multivessel CAD (n = 2679 of 3390) and 86.8% had left anterior descending (LAD) stenosis (n = 3190 of 3677) (proximal in 46.8% [n = 1749 of 3739]). Participants undergoing ETT had greater frequency of 3-vessel CAD, LAD, and proximal LAD stenosis than participants undergoing stress imaging. Conclusions and Relevance The ISCHEMIA trial randomized an SIHD population with moderate or severe ischemia on stress testing, of whom most had multivessel CAD. Trial Registration ClinicalTrials.gov Identifier: NCT0147152