Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome : a systematic review and meta-analysis

Aims/hypothesis FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS. Methods A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis. Results A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10−11) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10−10). This translated into an approximately 3.3 kg/m2 increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations. Conclusions/interpretation The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS

Interaction of brain areas of visual and vestibular simultaneous activity with fMRI.

Static body equilibrium is an essential requisite for human daily life. It is known that visual and vestibular systems must work together to support equilibrium. However, the relationship between these two systems is not fully understood. In this work, we present the results of a study which identify the interaction of brain areas that are involved with concurrent visual and vestibular inputs. The visual and the vestibular systems were individually and simultaneously stimulated, using flickering checkerboard (without movement stimulus) and galvanic current, during experiments of functional magnetic resonance imaging. Twenty-four right-handed and non-symptomatic subjects participated in this study. Single visual stimulation shows positive blood-oxygen-level-dependent (BOLD) responses (PBR) in the primary and associative visual cortices. Single vestibular stimulation shows PBR in the parieto-insular vestibular cortex, inferior parietal lobe, superior temporal gyrus, precentral gyrus and lobules V and VI of the cerebellar hemisphere. Simultaneous stimulation shows PBR in the middle and inferior frontal gyri and in the precentral gyrus. Vestibular- and somatosensory-related areas show negative BOLD responses (NBR) during simultaneous stimulation. NBR areas were also observed in the calcarine gyrus, lingual gyrus, cuneus and precuneus during simultaneous and single visual stimulations. For static visual and galvanic vestibular simultaneous stimulation, the reciprocal inhibitory visual-vestibular interaction pattern is observed in our results. The experimental results revealed interactions in frontal areas during concurrent visual-vestibular stimuli, which are affected by intermodal association areas in occipital, parietal, and temporal lobes

Predictive saccades in children and adults: A combined fMRI and eye tracking study

<div><p>Saccades were assessed in 21 adults (age 24 years, SD = 4) and 15 children (age 11 years, SD = 1), using combined functional magnetic resonance imaging (fMRI) and eye-tracking. Subjects visually tracked a point on a horizontal line in four conditions: time and position predictable task (PRED), position predictable (pPRED), time predictable (tPRED) and visually guided saccades (SAC). Both groups in the PRED but not in pPRED, tPRED and SAC produced predictive saccades with latency below 80 ms. In task versus group comparisons, children’s showed less efficient learning compared to adults for predictive saccades (adults = 48%, children = 34%, p = 0.05). In adults brain activation was found in the frontal and occipital regions in the PRED, in the intraparietal sulcus in pPRED and in the frontal eye field, posterior intraparietal sulcus and medial regions in the tPRED task. Group–task interaction was found in the supplementary eye field and visual cortex in the PRED task, and the frontal cortex including the right frontal eye field and left frontal pole, in the pPRED condition. These results indicate that, the basic visuomotor circuitry is present in both adults and children, but fine-tuning of the activation according to the task temporal and spatial demand mature late in child development.</p></div

Activated regions in task × group interaction and the average signal variation.

<p>The between-group interaction contrast (on the left) in pPRED × SAC activation in (A) supplementary eye field, (B) frontal pole. Statistical images were thresholded using cluster determined by Z-score > 1.96 and corrected cluster significance threshold of p < 0.05. On the right: the average signal change plotted for groups of adults and children. Regions of interest (ROIs) were generated in three local maxima of between-groups interaction contrast (on the left. These ROIs were then used to extract the signal variation from the contrasts of task × baseline fixation in each group. (Acronyms: SEF–supplementary eye field; FP–frontal pole).</p

Group activations for tasks with predictable components compared with visually guided saccades.

<p>The activation pattern changed according to the tasks predictability. (A) Time/position predictable (PRED) was characterized by an increase in precentral sulcus/superior frontal sulcus and medial frontal lobe. (B) Position predictable (pPRED) the fronto-parietal and anterior cingulate cortex activation was most evident. (C) Time predictable (tPRED) activation was localized mainly in intraparietal sulcus and medial portions of the brain. (D) In children, only time predictable (tPRED) showed differential activation from SAC in frontal cortex. Statistical images were thresholded using cluster determined by Z-score > 1.96 and (corrected) cluster significance threshold of p < 0.05. The MNI coordinates of all activated clusters are described in Supplementary material (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0196000#pone.0196000.s001" target="_blank">S1 Table</a>). (Acronyms: FEF–frontal eye field; SEF—supplementary eye field; ACC–anterior cingulate cortex; IPS—intraparietal sulcus; dlPFC—dorsolateral prefrontal cortex; vlPFC—ventrolateral prefrontal cortex; FP–frontal pole).</p