Pairs Of Male Monozygotic Twins Research Articles

A late-life neurogenetic signature of exposure to combat stress – A monozygotic discordant twin study

Animal models suggest that experiencing high-stress levels induces changes in amygdalar circuitry and gene expression. In humans, combat exposure has been shown to alter amygdalar responsivity and connectivity, but abnormalities have been indicated to normalize at least partially upon the termination of stress exposure. In contrast, other evidence suggests that combat exposure continues to exert influence on exposed individuals well beyond deployment and homecoming, as indicated by longitudinal psychosocial evidence from veterans, and observation of greater health decline in veterans late in life. Accordingly, the experience of combat stress early in life may affect amygdalar responsivity late in life, a possibility requiring careful consideration of the confounding effects of aging, genetic factors, and symptoms of post-traumatic stress disorder. Here, we investigated amygdalar responsivity in a unique sample of 16 male monozygotic (MZ) twin pairs in their sixties, where one but not the other sibling had been exposed to combat stress in early adulthood. Forty years after combat experience, a generally blunted amygdalar response was observed in combat-exposed veterans compared to their non-exposed twin siblings. Spatial associations between these phenotypical changes and patterns of gene expression in the brain were found for genes involved in the synaptic organization and chromatin structure. Protein-protein interactions among the set of identified genes pointed to histone modification mechanisms. We conclude that exposure to combat stress early in life continues to impact brain function beyond the termination of acute stress and appears to exert prolonged effects on amygdalar function later in life via neurogenetic mechanisms.

DNA identification of monozygotic twins

This study details the differentiation of identical twins based on single mutational base differences. There were three pairs of male monozygotic (MZ) twins in this study. DNA samples from blood, a buccal swab or saliva from each individual were all initially genotyped using 22 autosomal STR and 27 Y-STR loci. Preliminary screening confirmed there were no differences in the STR data between each pair of MZ twins. Whole Genome Sequence (WGS) data were generated from DNA extracted from the three body fluids from each individual. Kinship coefficients with 0.4254, 0.4557 and 0.4543 from 3 twins were generated based on WGS data to further confirm that their relationship was that of MZ twins. The fastq data generated by the Illumina Hiseq 2000 between MZ twins were then treated as “normal” as opposed to “tumor” using commercially available software tools to identify mutational single base changes. Sanger DNA sequencing confirmed there were 1, 5 and 9 single base changes found in WGS data from each of the three MZ twin sets. There was individual variation in the mutational base changes when comparing data from the three body fluids. The methods used in this study to differentiate MZ twins based on WGS data can readily be performed in many operational forensic DNA laboratories using user friendly software.

Concomitant Coronary Artery Disease in Identical Twins: Case Report and Systematic Literature Review.

Coronary artery disease (CAD) is multifactorial and strongly affected by genetic, epigenetic and environmental factors. Several studies have reported development of concomitant CAD in identical twins. We report a case in which a pair of Caucasian male monozygotic twins presented almost concomitantly with acute coronary syndrome (ACS) and had concordant coronary anatomy and identical site of occlusion. We performed a systematic literature review of PubMed, Web Of Science and Scopus databases from inception until 28 February 2023 of case reports/case series reporting the concomitant development of CAD in monozygotic twins. We found 25 eligible case reports with a total of 31 monozygotic twin pairs (including the case from our center) suffering from CAD and presenting (most of them simultaneously) with ACS (mean age of presentation: 45 ± 12 years, males: 81%). Coronary angiograms demonstrated lesion and anatomy concordance in 77% and 79% of the twin pairs, respectively. Screening for disease-related genetic mutations was performed in six twin pairs leading to the identification of five CAD-related genetic polymorphisms. This is the first systematic literature review of studies reporting identical twin pairs suffering from CAD. In summary, there is high concordance of coronary anatomy and clinical presentation between monozygotic twins. Future monozygotic twin studies-unbiased by age effects-can provide insights into CAD heritability being able to disentangle the traditional dyad of genetic and environmental factors and investigate the within-pair epigenetic drift.

Assisted Reproduction and Discussion of Rare Cases in Monozygotic Twinning.

Assisted reproductive technology is a crucial factor that increases the incidence of monozygotic twinning in humans. This article discusses the impact of various indicators in assisted reproductive technology studies on pregnancy outcomes, especially studies with a large number of clinical cases. Furthermore, three rare cases in multiples pregnancy are discussed: fetus papyraceous of a pair of male monozygotic twins in a set of triplets, two pairs of sesquizygotic twins with sex-discordance, and rare conjoined triplets.

Transcriptomic Differences Between Monozygotic Adolescent Twins Discordant For Metabolic Syndrome Following Weight Loss: A Case Study.

This case reports peripheral blood mononuclear cell (PBMC) transcriptomic changes in a pair of male monozygotic pediatric twins with metabolic syndrome (MetS) undertaking assisted weight loss. These 14-year-old boys presented with similar baseline biochemistry and body composition. After a 16-week weight-loss intervention, percent body weight loss was similar (Twin A 12%, and Twin B 13%). MetS resolved in Twin A but Twin B maintained elevated triglycerides after weight loss. Analysis of the PBMC transcriptome before and after weight loss revealed very different changes in gene expression including differences in the direction of expression of genes related to immune cell activation. 48.7% of genes that were downregulated in Twin A were upregulated in Twin B. This case highlights a novel approach to report the influence of chronic low-grade inflammation and metabolic dysfunction on the PBMC transcriptome. It explores whether expression of genes related to immune functions may underlie the differences in response to weight loss or whether transcriptomic alterations in immune cells may precede more traditional biomarkers of chronic pro-inflammation. These monozygotic twins present an example of divergence of phenotypic outcomes despite identical genetic background and similar treatment response.

Concordance of keratoconus in monozygotic twins before and after combined corneal crosslinking/photorefractive keratectomy (Athens Protocol) using Scheimpflug and OCT tomography.

To describe the concordance of keratoconus (KC) expression in 2 pairs of monozygotic twins before and after a combined corneal crosslinking (CXL)/photorefractive keratectomy (PRK) procedure. Private ambulatory eye surgery unit. Retrospective interventional twin study. Two pairs of male monozygotic twins with KC were studied retrospectively. Improvement of flattest (K1) and steepest (K2) keratometry, index of height decentration (IHD), and corneal thickness at the thinnest point and corneal epithelial thickness measured by anterior segment optical coherence tomography and Scheimpflug tomography was compared between respective eyes of monozygotic twin siblings 1 to 5 years after the application of combined CXL and topography-guided PRK of part of the refractive error (the Athens Protocol). Significant improvement was noted in all the keratometric indices of all 8 eyes after the combined CXL/PRK procedure. The difference in K1, K2, IHD, corneal thickness at the thinnest point, and corneal epithelial thickness percentage improvement between the right eyes of each pair of twins was statistically significant 1 year and 5 years postoperatively (P < .05). Statistically significant discordance in the aforementioned parameters percentage improvement was similarly observed between the left eyes of each pair of twins (P < .05). Although a genetic predisposition in KC is well documented, the discordance in keratometric indices improvement after a CXL/PRK procedure between respective eyes of monozygotic twins suggests that environmental influences may contribute to the disease expression as well. Variable degree of synergy in a combined CXL/PRK procedure may also explain the aforementioned discordant improvement.

Investigation of Skeletal Muscle Mitochondrial Function Following an Ultramarathon: A Case Study in Monozygotic Twins

The primary objective of this case study was to investigate the changes in skeletal muscle mitochondria that occur in response to a 100-km ultramarathon in monozygotic twins. Secondarily, we sought to determine if periodically consuming a low-carbohydrate, high-fat diet (LCHFD) during training would affect these changes. To accomplish these objectives, one pair of male monozygotic twins ran 100 km side-by-side on treadmills. During 8 weeks of training leading up to this event, twin 1 (T1) and twin 2 (T2) consumed a calorie and macronutrient-matched, high-carbohydrate diet, with the exception of 2 consecutive days per week for the final 4 weeks where T2 consumed a calorie and protein-matched LCHFD. Training load was matched between the subjects, most of which they completed together. The subjects were extremely well-matched in VO2 max (61.2 and 60.3 ml/kg/min), BMI (20.4 and 20.6 kg/m2), and body mass (62 and 61.9 kg). During the 100-km run, food and fluid intake were matched, as well as the pace of the run. The run took 16 hours and 3 minutes to complete. Blood draws and muscle biopsies from the vastus lateralis were collected 4 weeks prior to the run, as well as 4- and 52-hours post-run. During the last 4 weeks of training, T2 lost an average of ~1 kg of body weight (BW) over the two days of LCHFD each week (comparing BW of 4 consecutive Mondays to Wednesdays, p=0.02), which was regained two days after reintroduction of carbohydrate, consistent with fluctuating glycogen levels. Though T2 trained with periodically low glycogen levels, respiratory-exchange ratio was no different from T1 throughout the 100-km run. Four hours post-run, state 3, uncoupled, and fatty acid-supported mitochondrial respiration were reduced in T1 by 22.3%, 34.1% and 25.7%, respectively, and by 28.4%, 49.4% and 39.9% in T2, which was associated with a decrease of 15-20% in citrate synthase (CS) activity. Both twins exhibited decreases in mitochondrial complex proteins, though this was more marked in T2. Blood CPK, CRP, and AST levels were also elevated post-run. Possibly the most novel finding from this study was that 52 hours post-run, respiratory capacity, mitochondrial proteins, CS activity and blood markers showed signs of rapid recovery. It is currently unclear by what mechanism mitochondrial respiration and content was reduced 4 hours post-run, or how it recovered in 2 days. Interestingly, maximal mitochondrial ROS production (glutamate, malate and succinate-supported) was decreased post-run at both timepoints but was increased compared to baseline with the addition of ADP (12.5 μM – 100 μM). This suggests that the mitochondria were less sensitive to ADP-induced reductions in ROS. Neither diet resulted in better preservation of mitochondrial function 4-hours post-run, though T2 showed some signs of supercompensation 52 hours-post run. This study is valuable because it provides evidence of an acute reduction in mitochondrial content and function following ultra-endurance activity, followed by rapid recovery. This study was approved by the Brigham Young University Institutional Review Board and conformed to the principles of human experimentation set by the Declaration of Helsinki.

Twins Living Apart: Behavioral Insights/Twin Study Reviews: Managing Monochorionic-Diamniotic Twin Pregnancies; Paternity Testing in Multiple Pregnancies; Twin Research on Resilience; Trisomies in Twin Pregnancies/Human Interest: Reunited Brazilian Twins; Website for Twins with Disabled Co-Twins; Twins Separated in Secret of the Nile Series; Mengele: Unmasking the Angel of Death; Twins Helping Others.

A brief review of research findings regarding twins living apart is presented. This review is followed by a look into the lives of a pair of monozygotic male twins who have lived in different continents for many years, but who stay closely connected. The reasons behind their decision and its impact on their behavioral resemblance and social relationship quality are examined. The next section summarizes recent studies that address the management of monochorionic-diamniotic twin pregnancies, paternity testing in multiple pregnancies, trisomies in twin pregnancies and the roots of resilience. The final portion of this article presents human-interest stories involving reunited Brazilian twins, a new resource for twins with disabled co-twins, twins separated in the Secret of the Nile television series, a new book about Dr Josef Mengele and his horrific twin experiments conducted at the Auschwitz-Birkenau concentration camp, and a pair of twins dedicated to helping others.

Twin Data: The Lives That Drive the Findings/Twin Research Reviews: Twin Concordance for Kleine-Levin Syndrome; Twin Study of Political Discussion; Twin Relationship Quality and Urinary Cortisol Level; Twin Research Guide/In the News: Twins' Same Day Deliveries; Death of a Twin Holocaust Survivor; Identical Vindman Twins; Twin Festival in France; Tiniest Twins.

Twin data and the results generated by research are driven by the behavioral and physical attributes of twin participants. However, many investigators working with twin data have limited personal contact with actual twin-pairs. This situation may be limiting with respect to interpretation of results and formulation of new hypotheses. In an attempt to rectify this issue, key aspects of the interconnected lives of co-twins in three monozygotic male twin-pairs are presented. The section that follows includes a review of twin research on Kleine-Levin syndrome, political discussion, twin relationship quality and urinary cortisol level, and guidelines for determining sample sizes. The final part of this report presents twin-related news items relating to twins' same day deliveries, death of a twin Holocaust survivor, the Vindman twins, a twin festival in France and the tiniest twins on record.

Fat oxidation at rest and during exercise in male monozygotic twins

PurposeWe aimed to investigate if hereditary factors, leisure-time physical activity (LTPA) and metabolic health interact with resting fat oxidation (RFO) and peak fat oxidation (PFO) during ergometer cycling.MethodsWe recruited 23 male monozygotic twin pairs (aged 32–37 years) and determined their RFO and PFO with indirect calorimetry for 21 and 19 twin pairs and for 43 and 41 twin individuals, respectively. Using physical activity interviews and the Baecke questionnaire, we identified 10 twin pairs as LTPA discordant for the past 3 years. Of the twin pairs, 8 pairs participated in both RFO and PFO measurements, and 2 pairs participated in either of the measurements. We quantified the participants’ metabolic health with a 2-h oral glucose tolerance test.ResultsFat oxidation within co-twins was correlated at rest [intraclass correlation coefficient (ICC) = 0.54, 95% confidence interval (CI) 0.15–0.78] and during exercise (ICC = 0.67, 95% CI 0.33–0.86). The LTPA-discordant pairs had no pairwise differences in RFO or PFO. In the twin individual-based analysis, PFO was positively correlated with the past 12-month LTPA (r = 0.26, p = 0.034) and the Baecke score (r = 0.40, p = 0.022) and negatively correlated with the area under the curve of insulin (r = − 0.42, p = 0.015) and glucose (r = − 0.31, p = 0.050) during the oral glucose tolerance test.ConclusionsHereditary factors were more important than LTPA for determining fat oxidation at rest and during exercise. Additionally, PFO, but not RFO, was associated with better metabolic health.

Association Between Cardiovascular Health and Cognitive Performance: A Twins Study.

The 2020 Strategic Impact Goal introduced by the American Heart Association (AHA) aims at improving cardiovascular health (CVH) of all Americans by 20%. AHA defined ideal CVH across seven established modifiable risk factors for cardiovascular diseases. Prior studies have indicated that ideal CVH also benefits brain health and cognitive aging, but it is possible that this association is explained by familial factors. We examined 272 male monozygotic and dizygotic twin pairs (total 544 subjects) free of overt cardiovascular disease and dementia from the Vietnam Era Twin Registry. Memory and learning were measured by Trail Making tests and Wechsler Memory Scale (Immediate and Delayed Memory tests and Visual Reproductive Test). Each of the seven CVH components (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and blood glucose) was scored per established criterion. The mean age of the twins was 55 years, 96% were whites, and 61% monozygotic. When considering twins as individuals, for every unit increase in CVH score (indicating better cardiovascular health), twins demonstrated faster cognitive processing speed (Trail B: - 5.6 s, 95% CI - 10.3, - 0.9; p = 0.03) and better story recall, both immediate (0.35, 95% CI 0.06, 0.62; p = 0.02) and delayed (0.39, 95% CI 0.08, 0.70; p = 0.01). Better CVH is associated with better cognitive health in several domains. As suggested by within-pair analysis, this association is largely explained by familial factors, implying that early life exposures are shared determinants of both brain health and cardiovascular health.

Eye Refraction in Doubly Exchanged Monozygotic Twins.

This case study examined the hypothesis that longer outdoor time results in normal vision and refractive status, using unique genetically informative kinships. The participants were the members of 29-year-old doubly exchanged monozygotic male twin pairs from Bogotá, Colombia, in South America. Comprehensive ophthalmological examinations, including uncorrected and corrected visual acuity, refraction and keratometry, and visual life history interviews were undertaken; all examinations were conducted by two ophthalmologists blind to the hypothesis, relatedness, and rearing status of the four participants. Normal uncorrected vision and refractive status were present in the two rural-raised, unrelated brothers, relative to their urban-raised counterparts. Uncorrected visual acuities were 20/160 and 20/200 for the city-raised twins and 20/20 and 20/30 for the country-raised twins. Premature birth, low birth weight, computer use, and reading time could not explain these differences. It was concluded that time spent outdoors appears to be a significant factor in the development of myopia, reinforcing extant findings via a novel experimental approach.

Performing Together: Monozygotic Twin Comedians/Twin research: Mirror-Image Cleft Lip and Palate; Dental Caries; Noninvasive Prenatal testing; Capgras Syndrome with Folie à Deux/In the News: Athletic Twins; Transgendered Twins; Crib-Sharing; Common Careers.

Twin studies have shown that our sense of humor has an underlying genetic component, but less investigation of the origins of stand-up comedy has been undertaken. This article briefly reviews twin research findings on humor, then describes the working partnership and social affiliation of a pair of monozygotic male twins who perform together as stand-up comedians. The abilities, personalities and temperaments of these twins suggest future avenues for research in this interesting area. Next, findings from twin studies and case reports of twins with cleft lip and palate, dental caries, noninvasive prenatal testing and Capgras syndrome (with folie à deux) are summarized. In conclusion, recent news about athletic twins, transgendered twins, crib-sharing and career choice are presented.

COULD RAPIDLY MUTATING Y-STRS BE A POTENTIAL FORENSIC TOOL IN DISCRIMINATING LEBANESE MONOZYGOTIC TWINS?

Despite the high power of discrimination that characterizes the well identified 16 to 24 autosomal short tandem repeat markers, monozygotic twins differentiation is generally limited. Arising from a single fertilized egg, monozygotic twins share the same genotype therefore the same DNA profile. This situation imposes a challenge in forensics especially considering that lineage markers are in general less informative than autosomal ones. Although in some cases Y haplotype is considered a powerful investigative tool, it cannot distinguish males belonging to the same paternal lineage. The use of rapidly mutating Y-STRs with mutation rate above 1x10-2 that were recently included in forensic casework is presumed helpful. Since science is always dynamic and each population has its own characteristics, we aim in this study to distinguish between Lebanese monozygotic male twins using rapidly mutating Y-STRs. For this purpose, fourteen unrelated pairs of male monozygotic twins were recruited. Participants filled in a well-designed questionnaire and signed an informed consent. DNA was extracted using PureLink Genomic DNA Mini kit, genotyped using the Identifiler Plus kit, and separated on 3500 Genetic Analyzer to confirm the monozygosity status. DNA samples underwent a second amplification using the Y Filer Plus kit. According to our results, all the Y Filer Plus DNA profiles showed complete match for each twin pair. By consequence, the use of rapidly mutating Y-STRs in this study did not improve discrimination.

Muscle health and performance in monozygotic twins with 30 years of discordant exercise habits.

Physical health and function depend upon both genetic inheritance and environmental factors (e.g., exercise training). To enhance the understanding of heritability/adaptability, we explored the skeletal muscle health and physiological performance of monozygotic (MZ) twins with > 30 years of chronic endurance training vs. no specific/consistent exercise. One pair of male MZ twins (age = 52 years; Trained Twin, TT; Untrained Twin, UT) underwent analyses of: (1) anthropometric characteristics and blood profiles, (2) markers of cardiovascular and pulmonary health, and (3) skeletal muscle size, strength, and power and molecular markers of muscle health. This case study represents the most comprehensive physiological comparison of MZ twins with this length and magnitude of differing exercise history. TT exhibited: (1) lower body mass, body fat%, resting heart rate, blood pressure, cholesterol, triglycerides, and plasma glucose, (2) greater relative cycling power, anaerobic endurance, and aerobic capacity (VO2max), but lower muscle size/strength and poorer muscle quality, (3) more MHC I (slow-twitch) and fewer MHC IIa (fast-twitch) fibers, (4) greater AMPK protein expression, and (5) greater PAX7, IGF1Ec, IGF1Ea, and FN14 mRNA expression than UT. Several measured differences are the largest reported between MZ twins (TT expressed 55% more MHC I fibers, 12.4ml/kg/min greater VO2max, and 8.6% lower body fat% vs. UT). These data collectively (a) support utilizing chronic endurance training to improve body composition and cardiovascular health and (b) suggest the cardiovascular and skeletal muscle systems exhibit greater plasticity than previously thought, further highlighting the importance of studying MZ twins with large (long-term) differences in exposomes.

Whole‐genome DNA hydroxymethylation among monozygotic twins discordant for cardiovascular death: the prospective National Heart, Lung, and Blood Institute (NHLBI) Twin Study

ObjectivesEpigenetic modifications are related to cardiovascular disease. It is unknown whether DNA hydroxymethylation is associated with the risk for cardiovascular death that is independent of genes and common environment. This study aims to address this issue.Methods19 male monozygotic twin pairs middle‐aged in 1969–1973 and discordant for cardiovascular death through December 31, 2014 were included from the prospective National Heart, Lung, and Blood Institute Twin Study. Buffy coat leukocyte DNA samples were collected in 1986–87. Genome‐wide DNA hydroxymethylation levels were quantified using the hMe‐Seal‐seq. The log2 transformed reads were used for analysis of differentially hydroxymethylated regions (DhMRs) across the genome. Benjamini‐Hochberg false discovery rate (q value) of 0.05 was considered as the significance level. The bioinformatic tools Enrichr with Gene Ontology (GO) and the Cytoscape software package were used to analyze biological functions.ResultsThere were 73,311 statistically significant DhMRs after controlling for age and blood cell subtypes (q&lt;0.05 for all DhMRs). These DhMRs were located on all 22 autosomal chromosomes, and both the X and Y chromosomes. Among them, 27% of DhMRs were hypo‐hydroxymethlyated, had a log2 fold change ranging from −15.1 to −0.18, and were within/overlapped with 3′‐UTR (1.2%), 5′‐UTR (0.1%), exon (2.1%), intergenic regions (35.8%), intron (55.6%), non‐coding regions (0.6%), promoter transcription start sites (TSS) (2.4%), transcription terminal site (TTS) (2.1%); while 73% DhMRs were hyper‐hydroxymethylated, had a log2 fold change ranging from 0.14 to 15.7, and were within/overlapped with 3′‐UTR (0.9%), 5′‐UTR (0.1%), exon (1.7%), intergenic regions (49.2%), intron (44.9%), non‐coding regions (0.6%), promoter transcription start sites (TSS) (1.4%), and transcription terminal site (TTS) (1.2%). Using either all DhMRs with q value &lt;0.05, a multi‐dimensional scaling plot demonstrated the complete distinction of case twins from control twins along dimension 1 but not dimension 2. A total of 12 significant GO biological processes (p‐value &lt; 0.01) were identified. Cytoscape clustered the GO terms in these processes into 4 groups: target of rapamycin (TOR) signaling, metabolic process, cholesterol transport, and intracellular transport.ConclusionsDifferentially hydroxymethylated regions are prospectively related to cardiovascular death independent of genes and common environment.Support or Funding InformationNHLBI 1R21HL127368‐01 and Des Moines University Faculty Research Fund to Dr. DaiThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract P055: Methylation Levels at Growth Differentiation Factor- 15 Related Cpg Sites Are Not Related to Death Risk From Cardiovascular Disease Among Monozygotic Male Twins Discordant for Cardiovascular Disease: National Heart, Lung, and Blood Institute Twin Study

Background: Growth differentiation factor- 15 (GDF-15) is positively associated with the risk of mortality from acute coronary syndrome and chronic heart failure. A prior study reported decreased methylation at four promising GDF-15 related CpG sites tended to be associated with myocardial infarction, however, little is known of the association of methylation levels at these sites with the risk for cardiovascular disease (CVD) death. Objective: To evaluate whether methylation levels at the four GDF-15 CpG sites (site A: cg13033585, site B: cg16936953, site C: cg17150809, and site D: cg18608055) are associated with death from CVD, independent of genes and shared environmental factors. Method: We included 19 male monozygotic twin pairs discordant for death from CVD through December 31, 2014 from the National Heart, Lung, and Blood Institute (NHLBI) Twin Study initiated in 1969-1973. Buffy coat DNA samples were collected in exam 3 (1986-87). The vital status was followed up through December 31, 2014. Genome wide DNA methylation levels were quantified using the Illumina Infinium HumanMethylation450 (450K) BeadChip. Conditional logistic models were used to estimate hazard ratio (HR). Known baseline CVD risk factors were adjusted. Results: The twins’ mean baseline age was 50.4 years with standard deviation of 2.4. The crude HR was 0.01 (95% CI: 0.00, 2854.46), 2038.89 (95%CI: 0.01, 3.84 X 10 8 ), 0.12 (95% CI: 0.00, 55.99), and 2.08 (95% CI: 0.00, 1.26 X 10 6 ) for sites A, B, C, and D, respectively, suggesting that our sample size was small to test these sites. After adjustment for body mass index, years of education, and Framingham risk scores, HR was 0.03 (95% CI: 0.00, 45281.06) for site A, 700.96 (95% CI: 0.00, 2.32 X10 8 ) for site B, 0.00 (95% CI: 0.00, 7.35) for site C, and 0.81 (95% CI: 0.00, 1.44 X 10 6 ) for site D. Further adjustment for white blood cell subtypes dramatically changed HRs and/or largely widened 95% CIs, suggesting potential overadjustment bias: 0.01 (95% CI:0.00, 1.89 X 10 10 ) for site A, 2.78 X 10 8 (95% CI: 0.00, 7.84 X 10 21 ) for site B, 0.00 (95% CI: 0.00, 620.94) for site C, and 1.69 (95% CI: 0.00, 4.18 X 10 13 ) for site D. Conclusion: DNA methylation levels at the GDF-15 CpG sites are not associated with death risk from cardiovascular disease independent of genes and shared environment.

Metabolism of sex steroids is influenced by acquired adiposity—A study of young adult male monozygotic twin pairs

Obesity and ageing are associated with lower serum testosterone levels in men. How fat distribution or adipose tissue metabolism, independent of genetic factors and age, are related to sex steroid metabolism is less clear. We studied the associations between adiposity and serum sex hormone concentrations, and mRNA expression of genes regulating sex hormone metabolism in adipose tissue in young adult male monozygotic (MZ) twin pairs. The subjects [n=18 pairs; mean age, 32 years; individual body mass indexes (BMIs) 22–36kg/m2] included 9 male MZ twin pairs discordant for BMI [intra-pair difference (Δ) in BMI ≥3kg/m2]. Sex steroid concentrations were determined by liquid chromatography–tandem mass spectrometry, body composition by dual-energy X-ray absorptiometry and magnetic resonance imaging, and mRNA expressions from subcutaneous adipose tissue by Affymetrix. In BMI-discordant pairs (mean ΔBMI=5.9kg/m2), serum dihydrotestosterone (DHT) was lower [mean 1.9 (SD 0.7) vs. 2.4 (1.0) nmol/l, P=0.040] and mRNA expressions of DHT-inactivating AKR1C2 (P=0.021) and cortisol-producing HSD11B1 (P=0.008) higher in the heavier compared to the leaner co-twins. Serum free 17β-estradiol (E2) was higher [2.3 (0.5) vs. 1.9 (0.5) pmol/l, P=0.028], and in all twin pairs, serum E2 and estrone concentrations were higher in the heavier than in the leaner co-twins [107 (28) vs. 90 (22) pmol/l, P=0.006; and 123 (43) vs. 105 (27) pmol/l, P=0.025]. Within all twin pairs, i.e. independent of genetic effects and age, 1) the amount of subcutaneous fat inversely correlated with serum total and free testosterone, DHT, and sex hormone-binding globulin (SHBG) concentrations (P<0.01 for all), 2) intra-abdominal fat with total testosterone and SHBG (P<0.05), and 3) liver fat with SHBG (P=0.006). Also, 4) general and intra-abdominal adiposity correlated positively with mRNA expressions of AKR1C2, HSD11B1, and aromatase in adipose tissue (P<0.05). In conclusion, acquired adiposity was associated with decreased serum DHT and increased estrogen concentrations, independent of genetic factors and age. The reduction of DHT could be linked to its increased degradation (by AKR1C2 and HSD11B1) and increased estrogen levels to increased adiposity-related expression of aromatase in adipose tissue.

Somatosensory Brain Function and Gray Matter Regional Volumes Differ According to Exercise History: Evidence from Monozygotic Twins.

Associations between long-term physical activity and cortical function and brain structure are poorly known. Our aim was to assess whether brain functional and/or structural modulation associated with long-term physical activity is detectable using a discordant monozygotic male twin pair design. Nine monozygotic male twin pairs were carefully selected for an intrapair difference in their leisure-time physical activity of at least three years duration (mean age 34±1years). We registered somatosensory mismatch response (SMMR) in EEG to electrical stimulation of fingers and whole brain MR images. We obtained exercise history and measured physical fitness and body composition. Equivalent electrical dipole sources of SMMR as well as gray matter (GM) voxel counts in regions of interest indicated by source analysis were evaluated. SMMR dipolar source strengths differed between active and inactive twins within twin pairs in postcentral gyrus, medial frontal gyrus and superior temporal gyrus and in anterior cingulate (AC) GM voxel counts differed similarly. Compared to active twins, their inactive twin brothers showed greater dipole strengths in short periods of the deviant-elicited SMMR and larger AC GM voxel counts. Stronger activation in early unattended cortical processing of the deviant sensory signals in inactive co-twins may imply less effective gating of somatosensory information in inactive twins compared to their active brothers. Present findings indicate that already in 30's long-term physical activity pattern is linked with specific brain indices, both in functional and structural domains.

Effects of Light-Emitting Diode Therapy on Muscle Hypertrophy, Gene Expression, Performance, Damage, and Delayed-Onset Muscle Soreness: Case-control Study with a Pair of Identical Twins.

The aim of this study was to verify how a pair of monozygotic twins would respond to light-emitting diode therapy (LEDT) or placebo combined with a strength-training program during 12 weeks. This case-control study enrolled a pair of male monozygotic twins, allocated randomly to LEDT or placebo therapies. Light-emitting diode therapy or placebo was applied from a flexible light-emitting diode array (λ = 850 nm, total energy = 75 J, t = 15 seconds) to both quadriceps femoris muscles of each twin immediately after each strength training session (3 times/wk for 12 weeks) consisting of leg press and leg extension exercises with load of 80% and 50% of the 1-repetition maximum test, respectively. Muscle biopsies, magnetic resonance imaging, maximal load, and fatigue resistance tests were conducted before and after the training program to assess gene expression, muscle hypertrophy and performance, respectively. Creatine kinase levels in blood and visual analog scale assessed muscle damage and delayed-onset muscle soreness, respectively, during the training program. Compared with placebo, LEDT increased the maximal load in exercise and reduced fatigue, creatine kinase, and visual analog scale. Gene expression analyses showed decreases in markers of inflammation (interleukin 1β) and muscle atrophy (myostatin) with LEDT. Protein synthesis (mammalian target of rapamycin) and oxidative stress defense (SOD2 [mitochondrial superoxide dismutase]) were up-regulated with LEDT, together with increases in thigh muscle hypertrophy. Light-emitting diode therapy can be useful to reduce muscle damage, pain, and atrophy, as well as to increase muscle mass, recovery, and athletic performance in rehabilitation programs and sports medicine.