Angiotensin-converting enzyme ID polymorphism and fitness phenotype in the HERITAGE Family Study.

It has been suggested that genetic variation in the angiotensin-converting enzyme (ACE) gene is associated with physical performance. We studied the association between the ACE insertion (I)/deletion (D) polymorphism and several fitness phenotypes measured before and after 20 wk of a standardized endurance training program in sedentary Caucasian (n = 476) and black (n = 248) subjects. Phenotypes measured were oxygen uptake (VO(2)), work rate, heart rate, minute ventilation, tidal volume, and blood lactate levels during maximal and submaximal [50 W and at 60 and 80% of maximal VO(2) (VO(2 max))] exercise and stroke volume and cardiac output during submaximal exercise (50 W and at 60% VO(2 max)). The ACE ID polymorphism was typed with the three-primer PCR method. Out of 216 association tests performed on 54 phenotypes in 4 groups of participants, only 11 showed significant (P values from 0.042 to 0. 0001) associations with the ACE ID polymorphism. In contrast to previous claims, in Caucasian offspring, the DD homozygotes showed a 14-38% greater increase with training in VO(2 max), VO(2) at 80% of VO(2 max), and all work rate phenotypes and a 36% greater decrease in heart rate at 50 W than did the II homozygotes. No associations were evident in Caucasian parents or black parents or offspring. Thus these data do not support the hypothesis that the ACE ID polymorphism plays a major role in cardiorespiratory endurance.     

TGF-beta(1) gene-race interactions for resting and exercise blood pressure in the HERITAGE Family Study.

We examined the possible association between a transforming growth factor (TGF)-beta(1) gene polymorphism in codon 10 and blood pressure (BP) at rest, in acute response to exercise in the pretrained (sedentary) and trained states, as well as in its training response (Delta) to 20 wk of endurance exercise. Subjects were 257 black and 480 white, healthy sedentary normotensive subjects from the HERITAGE Family Study. The polymorphism was detected by polymerase chain reaction and digestion with the Msp A1 I endonuclease yielding a wild (leucine-10) and a mutant (proline-10) allele. Resting and exercise [50 W plus 60, 80, and 100% maximal oxygen consumption (VO(2)(max))] BP were determined before and after training. Significant (P < 0.05) race-genotype interactions were found for systolic (S) BP in both the sedentary and trained states. Among whites but not in blacks, the TGF-beta(1) genotypes were significantly (P < 0.05) associated with sedentary-state SBP at rest, at 50 W, and at 60 and 100% VO(2)(max)as well as with trained-state SBP at rest and at 80 and 100% VO(2)(max). The leucine-10 homozygotes had significantly (P < 0.05) lower SBP than proline-10 homozygotes. DeltaBP was not significantly associated with genotype. These results support the hypothesis of an association between the TGF-beta(1) marker in codon 10 and SBP at rest and in response to acute exercise in whites but not in blacks.     

Longitudinal Changes in Total Brain Volume in Schizophrenia: Relation to Symptom Severity,Cognition and Antipsychotic Medication

Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999–2001 at the age of 33–35 years. A follow-up was conducted 9 years later during 2008–2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.     

Masculinization of the eruption pattern of permanent mandibular canines in opposite sex twin girls

The aim of this study is to explore the effect of prenatal androgenization on the clinical eruption of permanent teeth expressing dimorphism and bimaturism. The eruption curves of permanent teeth (except third molars), including those that make up the canine complex (permanent canines, lower first premolars), are compared among opposite sex twins (OS twins) relative to single‐born boys and girls. The comparisons are made with regard to three phases of eruption (pierced mucosa, half‐ erupted, and completely erupted) from a cross‐sectional sample of dental casts, using Kaplan–Meier survival and Cox regression analyzes. The casts were collected from 2159 school children from the US Collaborative Perinatal Project, including 39 pairs of OS‐twins, of which 12 pairs (30.8%) were Euro‐Americans and 27 pairs (69.2%) were of African‐American ancestry. The eruption patterns of the incisors, upper first molars, and lower canines were found to be significantly masculinized (delayed) among OS twin girls. The differences in most other teeth were either not significant, or the number of observations of active eruption phases were too few, such as in the upper first molars and incisors, to yield strong evidence and meaningful results. The masculinization of the tooth eruption pattern in OS twin girls is intriguing because of the lower canine responses during puberty, as well as canine primordial formation during early fetal androgenization of their co‐twin during the 8th to 14th gestational weeks. The present results offer a challenge for future research exploring tooth eruption mechanisms, and may also highlight some cases of delayed or ectopic canines, which are biased toward females. Am J Phys Anthropol 151:566–572, 2013. © 2013 Wiley Periodicals, Inc.     

Positive and negative life changes and LDL cholesterol.

Epidemiological studies have revealed that stressful changes in social environment increase the risk of cardiovascular mortality. In this study, the influence of major negative and positive life changes on serum cholesterol was examined in middle-aged men to determine a possible biochemical link between life changes and cardiovascular mortality. The results showed no influence of negative life changes on serum cholesterols. However, positive life changes significantly predicted a reduction in total and LDL (low-density lipoprotein) cholesterol levels after adjustment for the baseline cardiovascular health status, baseline cholesterol level, diet, body mass index, waist-to-hip ratio and cardiorespiratory fitness. The odds ratio for lowering LDL cholesterol was 5.2 in the men reporting positive events compared with those reporting none. The findings suggest a predictive value of positive life changes for atherogenic lipid profile in middle-aged men.     

Association of lipin 1 gene polymorphisms with measures of energy and glucose metabolism

Objective: To examine the importance of lipin 1 (LPIN1) gene variation in energy and glucose metabolism. Transgenic animal models have shown that lipin, a protein encoded by the LPIN1 gene, promotes fat synthesis and storage in adipose tissue while decreasing energy expenditure and lipid oxidation in skeletal muscle. Lpin1 was identified as the mutated gene in the fatty liver dystrophy mouse, which exhibits lipin deficiency and features of human lipodystrophy. Research Methods and Procedures: We genotyped five LPIN1 polymorphisms and tested for association with resting metabolic rate (RMR), fat oxidation, fasting plasma insulin and glucose concentration, and obesity‐related phenotypes, including BMI, body fat percentage, sum of six skinfolds, and waist circumference in 712 subjects of the Quebec Family Study. Results: The strongest results were generation‐specific. In parents, RMR of the G/G IVS13 + 3333A>G homozygotes was 107 kcal/d higher than in A/A homozygotes and 39 kcal/d higher than in A/G heterozygotes (p = 0.0003). In offspring, carriers of the C allele of the IVS18 + 181C>T variant had significantly higher (p < 0.0003) insulin levels than T/T homozygotes. These associations remained significant after adjusting for multiple testing. Several other associations between body composition measures and the IVS18 + 181C>T variant were significant (p = 0.05 to 0.003), suggesting a strong pattern of relationships. Discussion: These findings support the hypothesis that sequence variation in the LPIN1 gene contributes to variation in RMR and obesity‐related phenotypes potentially in an age‐dependent manner.     

Intra-annual tracheid formation of Norway spruce provenances in southern Finland

We studied the intra-annual wood formation in a Norway spruce provenance experiment in southern Finland from 2004–2008. Two Finnish provenances, northern and southern, as well as German and Hungarian provenances were included. Timing of tracheid formation and differentiation, and tracheid dimensions were determined from periodically extracted microcores. The aim was to determine the differences between the years and provenances in the timing of the xylogenesis and in the xylem characteristics. Year-to-year variation was high both in timing of tracheid formation and xylem characteristics, while between-provenance differences were small. The onset of tracheid formation varied from early May to late June in different trees in different years. The onset of tracheid formation was not closely related to the annual variations of temperature sum. In all the years, daily temperatures exceeded the threshold +5°C for several weeks before the onset of tracheid formation. The highest tracheid formation rate occurred after the summer solstice in all years and generally coincided with the highest daily temperatures during the growing season. Tracheid production ceased early in 2006 due to a mid-summer drought. Cell differentiation continued late in autumn as non-mature tracheids were still observed around mid-September. No clear differences between the provenances in the timing of tracheid formation were observed, although the Finnish provenances tended to initiate tracheid formation slightly earlier than the other provenances. The tree-ring widths of the Finnish provenances were also wider, while tracheid diameter of the German provenance was slightly smaller. Our results indicate that between-tree variation in the timing of wood formation is high compared with the latitude effect of seed source.