11 research outputs found
The maternal environment programs postnatal weight gain and glucose tolerance of male offspring, but placental and fetal growth are determined by fetal genotype in the Leprdb/+ model of gestational diabetes
Mice heterozygous for a signaling-deficient leptin receptor (Leprdb/+ [db/+]) are widely used as a model of gestational diabetes that results in poor fetal outcomes. This study investigated the importance of fetal genotype (db/+) relative to abnormal maternal metabolism for placental function and therefore fetal growth and offspring health. Wild-type (WT) and db/+ females were mated to db/+ and WT males, respectively, generating litters of mixed genotype. Placentas and fetuses were weighed at embryonic day 18.5; offspring weight, hormone levels, glucose tolerance, and blood pressure were assessed at 3 and 6 months. Pregnant db/+, but not WT, dams had impaired glucose tolerance. The db/+ placentas and fetuses were heavier than WT, but the maternal environment had no effect; WT placentas/fetuses from db/+ mothers were no bigger than WT placentas/fetuses carried by WT mothers. Postnatal weight gain, glucose metabolism, and leptin levels were all influenced by offspring genotype. However, maternal environment affected aspects of offspring health because WT male offspring born to db/+ dams were heavier and had worse glucose tolerance than the sex-matched WT offspring of WT mothers. Blood pressure was not affected by maternal or offspring genotype. These data reveal that studies using the db/+ mouse to model outcomes of pregnancy complicated by gestational diabetes should be mindful of the genetically predisposed fetal/postnatal overgrowth. Although inappropriate for dissecting the effect of maternal hyperglycemia on the contribution of placental function to macrosomia, the db/+ mouse may prove useful for investigating mechanisms underlying programming of suboptimal postnatal weight gain and glucose metabolism by an adverse maternal metabolic environment
Forest plot for meta-analysis on the association between ever active tobacco smoking and adult onset asthma, without including the genetic effect.
<p>Forest plot for meta-analysis on the association between ever active tobacco smoking and adult onset asthma, without including the genetic effect.</p
Study populations included in GWI study on active smoking and adult onset asthma.
<p>Study populations included in GWI study on active smoking and adult onset asthma.</p
Forest plots for the meta-analysis and replication study on the genetic effect of SNP rs5011804 on chromosome 12 in subjects exposed and non-exposed to ever active tobacco smoking (identified in second approach).
<p>The bottom forest plot presents the interaction meta-analysis and replication study for this SNP. ORs are calculated using a fixed effect model.</p
Top SNPs that interact with active tobacco smoking in adult onset asthma identified in second approach (genetic effect in exposed)<sup>#</sup>.
<p>Top SNPs that interact with active tobacco smoking in adult onset asthma identified in second approach (genetic effect in exposed)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172716#t003fn001" target="_blank"><sup>#</sup></a>.</p
Top SNPs that interact with active tobacco smoking in adult onset asthma identified in both approaches<sup>#</sup>.
<p>Top SNPs that interact with active tobacco smoking in adult onset asthma identified in both approaches<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172716#t004fn001" target="_blank"><sup>#</sup></a>.</p
Genetic effect of SNP rs5011804 following an additive model in the LifeLines cohort (N = 12,475), stratified by different tobacco smoke exposures.
<p>Genetic effect of SNP rs5011804 following an additive model in the LifeLines cohort (N = 12,475), stratified by different tobacco smoke exposures.</p
Forest plots for the meta-analysis and replication study on the genetic effect of SNP rs9969775 on chromosome 9 in subjects exposed and non-exposed to ever active tobacco smoking (identified in first approach).
<p>The bottom forest plot presents the interaction meta-analysis and replication study for this SNP. ORs are calculated using a fixed effect model.</p
Top SNPs that interact with active tobacco smoking in adult onset asthma identified in first approach (overall interaction effect)<sup>#</sup>.
<p>Top SNPs that interact with active tobacco smoking in adult onset asthma identified in first approach (overall interaction effect)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172716#t002fn001" target="_blank"><sup>#</sup></a>.</p