BMI loci and longitudinal BMI from adolescence to young adulthood in an ethnically diverse cohort.

OBJECTIVE: The association of obesity susceptibility variants with change in body mass index (BMI) across the life course is not well understood. SUBJECTS: In ancestry-stratified models of 5962 European American (EA), 2080 African American (AA) and 1582 Hispanic American (HA) individuals from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examined associations between 34 obesity single-nucleotide polymorphisms (SNPs) with per year change in BMI, measured by the slope from a growth-curve analysis of two or more BMI measurements between adolescence and young adulthood. For SNPs nominally associated with BMI change (P<0.05), we interrogated age differences within data collection Wave and time differences between age categories that overlapped between Waves. RESULTS: We found SNPs in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 were significantly associated (P<0.0015≈0.05/34) with BMI change in EA and the ancestry-combined meta-analysis. rs9939609 in FTO met genome-wide significance at P<5e-08 in the EA and ancestry-combined analysis, respectively [Beta(se)=0.025(0.004);Beta(se)=0.021(0.003)]. No SNPs were significant after Bonferroni correction in AA or HA, although five SNPs in AA and four SNPs in HA were nominally significant (P<0.05). In EA and the ancestry-combined meta-analysis, rs3817334 near MTCH2 showed larger effects in younger respondents, whereas rs987237 near TFAP2B, showed larger effects in older respondents across all Waves. Differences in effect estimates across time for MTCH2 and TFAP2B are suggestive of either era or cohort effects. CONCLUSION: The observed association between variants in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 with change in BMI from adolescence to young adulthood suggest that the genetic effect of BMI loci varies over time in a complex manner, highlighting the importance of investigating loci influencing obesity risk across the life course.

Improved parental dietary quality is associated with children's dietary intake through the home environment.

BACKGROUND: Improving access to supermarkets has been shown to improve some dietary outcomes, yet there is little evidence for such effects on children. Relatedly, there is a dearth of research assessing the impact of a structural change (i.e. supermarket in a former food desert) on the home environment and its relationship with children's diet. OBJECTIVE: Assess the relative impact of the home environment on children's diet after the introduction of a new supermarket in a food desert. METHODS: Among a randomly selected cohort of households living in a food desert, parental diet was assessed before and after the opening of a full-service supermarket. The home environment and children's intake of fruits and vegetables was measured at one point - after the store's opening. Structural equation models were used to estimate the pathways between changes in parental dietary quality at follow-up and children's dietary intake through the home environment. RESULTS: Parental dietary improvement after the supermarket opened was associated with having a better home environment (ß = 0.45, p = 0.001) and with healthier children's dietary intake (ß = 0.46, p < 0.001) through higher family nutrition and physical activity scores (ß = 0.25, p = 0.02). CONCLUSIONS: Policy solutions designed to improve diet among low-resource communities should take into account the importance of the home environment.

Noise-stabilized random attractor.

A two-dimensional flow model is introduced with deterministic behavior consisting of bursts that become successively larger, with longer interburst time intervals between them. The system is symmetric in one variable and there are bursts on either side of , separated by the presence of an invariant manifold at . In the presence of arbitrarily small additive noise in the direction, the successive bursts have bounded amplitudes and interburst intervals. This system with noise is proposed as a model for edge-localized modes in tokamaks. With noise, the bursts can switch from positive to negative and vice versa. The probability distribution of burst heights and interburst periods is studied, as is the dependence of the statistics on the noise variance. The modification of this behavior as the symmetry in is broken is studied, showing qualitatively similar behavior if the symmetry breaking is small enough. Experimental observations of a nonlinear circuit governed by the same equations are presented, showing good agreement.

Influence of SNP*SNP interaction on BMI in European American adolescents: findings from the National Longitudinal Study of Adolescent Health.

BACKGROUND: Adolescent obesity is predictive of future weight gain, obesity and adult onset severe obesity (body mass index [BMI] ≥40 kg m(-2) ). Despite successful efforts to identify Single Nucleotide Polymorphisms (SNPs) influencing BMI, <5% of the 40-80% heritability of the phenotype has been explained. Identification of gene-gene (G-G) interactions between known variants can help explain this hidden heritability as well as identify potential biological mechanisms affecting weight gain during this critical developmental period. OBJECTIVE: We have recently shown distinct genetic effects on BMI across the life course, and thus it is important to examine the evidence for epistasis in adolescence. METHODS: In adolescent participants of European descent from wave II of the National Longitudinal Study of Adolescent Health (Add Health, n = 5072, ages 12-21, 52.5% female), we tested 34 established BMI-related SNPs for G-G interaction effects on BMI z-score. We used mixed-effects regression, assuming multiplicative interaction models adjusting for age, sex and geographic region, with random effects for family and school. RESULTS: For 28 G-G interactions that were nominally significant (P < 0.05), we attempted to replicate our results in an adolescent sample from the Childhood European American Cohort from Philadelphia. In the replication study, one interaction (PRKD1-FTO) was significant after correction for multiple testing. CONCLUSIONS: Our results are suggestive of epistatic effects on BMI during adolescence and point to potentially interactive effects between genes in biological pathways important in obesity.

The interaction between physical activity and obesity gene variants in association with BMI: Does the obesogenic environment matter?

Little is known about how obesity susceptibility single nucleotide polymorphisms (SNPs) interact with moderate to vigorous physical activity (MVPA) in relation to BMI during adolescence, once obesogenic neighborhood factors are accounted for. In race stratified models, including European (EA; N=4977), African (AA; N=1726), and Hispanic Americans (HA; N=1270) from the National Longitudinal Study of Adolescent to Adult Health (1996; ages 12-21), we assessed the evidence for a SNPxMVPA interaction with BMI-for-age Z score, once accounting for obesogenic neighborhood factors including physical activity amenities, transportation and recreation infrastructure, poverty and crime. Eight SNPxMVPA interactions with suggestive significance (p<0.10; three in each EA, and AA, two in HA) were observed showing attenuation on BMI-for-age Z score in adolescents with ≥5 versus <5 bouts/week MVPA, except for rs10146997 (near NRXN3). Findings were robust to the inclusion of neighborhood-level variables as covariates. These findings suggest that any attenuation from MVPA on a genetic susceptibility to obesity during adolescence is likely not operating through obesogenic neighborhood factors.

Caries-preventive effect of two concentrations of stannous fluoride mouthrinse.

The effectiveness of a stannous fluoride mouthrinse, when used once each school day, was investigated in a 3-year study. Effervescent stannous fluoride tablets of two concentrations were dissolved in 20 ml of water, giving solutions of 100 parts/10(6)F- and 200 parts/10(6)F- respectively. Approximately 1,200 children, with a mean age of 10 years, were divided on a random basis into three groups. Two of the groups rinsed with the two strengths of solution and the third group rinsed with a placebo. Examinations were carried out at the commencement of the study, and at yearly intervals thereafter. The final series was carried out a year after the rinsing procedures were terminated. There were significant reductions in the numbers of new caries in each of the two experimental groups as compared with the controls. The concentration of the solutions appeared to have little influence on the results. More dramatic reductions were noted in the teeth which erupted during the course of the study. A residual effect was demonstrated a year after the rinsing procedures were terminated.

A correlation study of diet, oral hygiene and dental caries in 457 Canadian children.

The interrelationship of diet, oral hygiene and caries was evaluated. Of the sample size of 457 children, 234 were in grade 1 and 223 grade 7. Five-day diet surveys were obtained, followed by clinical examinations for oral hygiene and caries. One examiner, using mouth mirror, explorer and extraoral light, conducted the caries examination. From the diet surveys, refined and total carbohydrate consumption was calculated per day; between meals, at meals, and totaled for the day. Five-day totals, which included one weekend, were recorded along with frequency of eating per day and for the 5-day periods. Computer analysis revealed no significant correlation between the diet variables and caries or oral hygiene indices and caries. The children with high caries indices did not have the poorest oral hygiene nor consume the most carbohydrates. Similarly, the children with low caries indices did not have the cleanest teeth nor consume lesser amounts of carbohydrates.

A clinical evaluation of occlusal composite and amalgam restorations: one- and two-year results.

A two-year study was conducted to compare the qualitative advantages, if any, of a conventional, cold-curing composite resin to amalgam in occlusal Class I cavities in posterior teeth. The composite was placed into modified, conservative cavity preparations using the acid etch technique. Sixty-one pairs of contralateral restorations were evaluated. Forty-six percent of the amalgams and 42.6% of the composites were considered sound. The major deficiency of each material was rough or chipped margins of the amalgams (38%) and worn surfaces of the composites (26%). The use of conservative cavity preparations and the acid-etch technique with bonding agent and final glaze improved the longevity of the composite restorations compared to previous studies. However, the improvement does not suggest that this method will have a long-term effect on clinical success nor does it indicate that composite is superior to amalgam other than in marginal integrity and esthetics.

Effect of cutting instruments on permeability and morphology of the dentin surface.

There are major differences in morphological detail after cutting the dentin surface among the methods commonly used to prepare dental cavities. The purpose of this study was to compare dentin permeability and the morphology of the dentin surfaces prepared with diamond and carbide steel burs after etching with 6% citric acid. Twenty-four freshly extracted human third molars were sectioned, mounted on plexiglass, and connected to the dentin-permeability measuring apparatus. The permeability of dentin was measured by fluid filtration and expressed as hydraulic conductance. There were two study groups of 12 teeth. Each tooth had one occlusal cavity preparation prepared but utilized three depths: the original was prepared just into the dentin, the second 0.5 mm deeper than the first, and the third 0.5 mm deeper than the second. One group had the first cavity prepared with a diamond, the second deepened using a steel bur, then the third depth was made by use of the diamond. The other group had the first cavity preparation prepared with a steel bur, deepened 0.5 mm again using a diamond, then deepened again using a steel bur. Dentin permeability was measured after cavity preparation, then after 2 minutes of acid etching. Analysis of variance and Duncan's multiple range test were used to establish whether differences were significant at the 0.05 confidence level. Prepared and acid-etched surfaces were characterized using a scanning electron microscope to identify any differences between the two groups. After acid etching with 6% citric acid, the permeability of dentin cavities prepared with diamond burs was significantly less than the permeability of cavities prepared with carbide steel burs. After etching, there were differences in the appearance of the dentin surfaces prepared with diamonds and steel burs. Dentin bonding agents may have their effectiveness reduced when placed following cavity preparation by use of a diamond.

Clinical evaluation of a restoration containing fluoride: two-year results.

Fluoride-containing restorations were placed on the distal surface of primary second molars to evaluate their effectiveness in controlling caries on the mesial surface of the approximating permanent first molars. A half-mouth study design was used with the control primary second molars in the same arch, either restored with amalgam or left sound. After two years, radiographs of 56 pairs of permanent first molars in 48 children were evaluated independently by three examiners blind to whether they were examining study or control surfaces. In 15 matched pairs, the study restoration had the effect of preventing a carious lesion on the mesial surface of a permanent first molar. In six matched pairs, the study restoration had the effect of not preventing progression of a carious lesion on the mesial surface of a permanent first molar. In 35 matched pairs, there was no effect observed. At the two-year evaluation, the study restorations with added fluoride controlled caries progression significantly on the adjacent mesial surfaces of permanent first molars when compared to the controls using the Sign test (P less than 0.05).

The association between childhood sexual and physical abuse with incident adult severe obesity across 13 years of the National Longitudinal Study of Adolescent Health.

BACKGROUND: Severe obesity has increased, yet childhood antecedents of adult severe obesity are not well understood. OBJECTIVE: Estimate adult-onset severe obesity risk in individuals with history of childhood physical and/or sexual abuse compared with those who did not report abuse. METHODS: Longitudinal analysis of participants from the US National Longitudinal Study of Adolescent Health (n = 10,774) wave II (1996; aged 12-22 years) followed through wave IV (2008-2009; aged 24-34 years). New cases of adult-onset severe obesity (body mass index [BMI] ≥ 40 kg/m2 using measured height and weight) in individuals followed over 13 years who were not severely obese during adolescence (BMI <120% of 95th percentile Centers for Disease Control and Prevention National Center for Health Statistics growth curves). RESULTS: The combined occurrence of self-reported sexual and physical abuse during childhood was associated with an increased risk of incident severe obesity in adulthood in non-minority females (hazard ratio [HR; 95% Confidence Interval] = 2.5; 1.3, 4.8) and males (HR = 3.6; 1.5, 8.5) compared with individuals with no history of abuse. CONCLUSION: In addition to other social and emotional risks, exposure to sexual and physical abuse during childhood may increase risk of severe obesity later in life. Consideration of the confluence of childhood abuse might be considered as part of preventive and therapeutic approaches to address severe obesity.

STIM1 and SLC24A4 Are Critical for Enamel Maturation.

Dental enamel formation depends upon the transcellular transport of Ca(2+) by ameloblasts, but little is known about the molecular mechanism, or even if the same process is operative during the secretory and maturation stages of amelogenesis. Identifying mutations in genes involved in Ca(2+) homeostasis that cause inherited enamel defects can provide insights into the molecular participants and potential mechanisms of Ca(2+) handling by ameloblasts. Stromal Interaction Molecule 1 (STIM1) is an ER transmembrane protein that activates membrane-specific Ca(2+) influx in response to the depletion of ER Ca(2+) stores. Solute carrier family 24, member 4 (SLC24A4), is a Na(+)/K(+)/Ca(2+) transporter that exchanges intracellular Ca(2+) and K(+) for extracellular Na(+). We identified a proband with syndromic hypomaturation enamel defects caused by a homozygous C to T transition (g.232598C>T c.1276C>T p.Arg426Cys) in STIM1, and a proband with isolated hypomaturation enamel defects caused by a homozygous C to T transition (g.124552C>T; c.437C>T; p.Ala146Val) in SLC24A4. Immunohistochemistry of developing mouse molars and incisors showed positive STIM1 and SLC24A4 signal specifically in maturation-stage ameloblasts. We conclude that enamel maturation is dependent upon STIM1 and SLC24A4 function, and that there are important differences in the Ca(2+) transcellular transport systems used by secretory- and maturation-stage ameloblasts.

Moderate to vigorous physical activity interactions with genetic variants and body mass index in a large US ethnically diverse cohort.

BACKGROUND: Little is known about the interaction between genetic and behavioural factors during lifecycle risk periods for obesity and how associations vary across race/ethnicity. OBJECTIVE: The objective of this study was to examine joint associations of adiposity-related single-nucleotide polymorphisms (SNPs) and moderate to vigorous physical activity (MVPA) with body mass index (BMI) in a diverse adolescent cohort. METHODS: Using data from the National Longitudinal Study of Adolescent Health (n = 8113: Wave II 1996; ages 12-21, Wave III; ages 18-27), we assessed interactions of 41 well-established SNPs and MVPA with BMI-for-age Z-scores in European Americans (EA; n = 5077), African-Americans (AA; n = 1736) and Hispanic Americans (HA; n = 1300). RESULTS: Of 97 assessed, we found nominally significant SNP-MVPA interactions on BMI-for-age Z-score in EA at GNPDA2 and FTO and in HA at LZTR2/SEC16B. In EA, the estimated effect of the FTO risk allele on BMI-for-age Z-score was lower (ß = -0.13; 95% confidence interval [CI]: 0.08, 0.18) in individuals with ≥5 vs. <5 (ß = 0.24; CI: 0.16, 0.32) bouts of MVPA per week (P for interaction 0.02). Race/ethnicity-pooled meta-analysis showed nominally significant interactions for SNPs at TFAP2B, POC5 and LYPLAL1. CONCLUSIONS: High MVPA may attenuate underlying genetic risk for obesity during adolescence, a high-risk period for adult obesity.

Screen time behaviours may interact with obesity genes, independent of physical activity, to influence adolescent BMI in an ethnically diverse cohort.

BACKGROUND: There has been little investigation of gene-by-environment interactions related to sedentary behaviour, a risk factor for obesity defined as leisure screen time (ST; i.e. television, video and computer games). OBJECTIVE: To test the hypothesis that limiting ST use attenuates the genetic predisposition to increased body mass index (BMI), independent of physical activity. DESIGN: Using 7642 wave II participants of the National Longitudinal Study of Adolescent Health, (Add Health; mean = 16.4 years, 52.6% female), we assessed the interaction of ST (h week(-1) ) and 41 established obesity single nucleotide polymorphisms (SNPs) with age- and sex-specific BMI Z-scores in 4788 European-American (EA), 1612 African-American (AA) and 1242 Hispanic American (HA) adolescents. RESULTS: Nominally significant SNP*ST interaction were found for FLJ35779 in EA, GNPDA2 in AA and none in HA (EA: beta [SE] = 0.016[0.007]), AA: beta [SE] = 0.016[0.011]) per 7 h week(-1) ST and one risk allele in relation to BMI Z-score. CONCLUSIONS: While for two established BMI loci, we find evidence that high levels of ST exacerbate the influence of obesity susceptibility variants on body mass; overall, we do not find strong evidence for interactions between the majority of established obesity loci. However, future studies with larger sample sizes, or that may build on our current study and the growing published literature, are clearly warranted.

Estimation of genetic effects on BMI during adolescence in an ethnically diverse cohort: The National Longitudinal Study of Adolescent Health.

OBJECTIVE: The contribution of genetic variants to body mass index (BMI) during adolescence across multiethnic samples is largely unknown. We selected genetic loci associated with BMI or obesity in European-descent samples and examined them in a multiethnic adolescent sample. DESIGN AND SAMPLE: In 5103 European American (EA), 1748 African American (AfA), 1304 Hispanic American (HA) and 439 Asian American (AsA) participants of the National Longitudinal Study of Adolescent Health (Add Health; ages 12-21 years, 47.5% male), we assessed the association between 41 established obesity-related single-nucleotide polymorphisms (SNPs) with BMI using additive genetic models, stratified by race/ethnicity, and in a pooled meta-analysis sample. We also compared the magnitude of effect for BMI-SNP associations in EA and AfA adolescents to comparable effect estimates from 11 861 EA and AfA adults in the Atherosclerosis Risk in Communities study (ages 45-64 years, 43.2% male). RESULTS: Thirty-five of 41 BMI-SNP associations were directionally consistent with published studies in European populations, 18 achieved nominal significance (P<0.05; effect sizes from 0.19 to 0.71 kg m(-2) increase in BMI per effect allele), while 4 (FTO, TMEM18, TFAP2B, MC4R) remained significant after Bonferroni correction (P<0.0015). Of 41 BMI-SNP associations in AfA, HA and AsA adolescents, nine, three and five, respectively, were directionally consistent and nominally significant. In the pooled meta-analysis, 36 of 41 effect estimates were directionally consistent and 21 of 36 were nominally significant. In EA adolescents, BMI effect estimates were larger (P<0.05) for variants near TMEM18, PTER and MC4R and smaller for variants near MTIF3 and NRXN3 compared with EA adults. CONCLUSION: Our findings suggest that obesity susceptibility loci may have a comparatively stronger role during adolescence than during adulthood, with variation across race/ethnic subpopulation.

Altered enamelin phosphorylation site causes amelogenesis imperfecta.

Defects in the enamelin gene (ENAM) cause amelogenesis imperfecta (AI). Our objective was to identify the genetic etiology of enamel hypoplasia in a Caucasian proband. Our hypothesis was that ENAM was defective. The proband and his father have an AG insertion (g.13185_13186insAG; p.422FsX448) in ENAM previously identified in AI kindreds from Slovenia and Turkey. The proband, his brother, and his mother have a novel missense mutation (g.12573C>T) that substitutes leucine for a phosphorylated serine (p.S216L) in the 32-kDa enamelin cleavage product. In this family, a defect in one ENAM allele caused minor pitting or localized enamel hypoplasia, whereas defects in both alleles caused severe enamel malformations, with little or no mineral covering dentin. Ser(216) is one of two serines on the 32-kDa enamelin that is phosphorylated by Golgi casein kinase and is thought to mediate calcium binding. We propose that phosphorylation of enamelin is critical for its function.