Association of a low density lipoprotein receptor microsatellite variant with obesity

OBJECTIVE To determine whether a microsatellite polymorphism located towards the 3' end of the low density lipoprotein receptor gene (LDLR) is associated with obesity. DESIGN A cross-sectional case-control study. SUBJECTS One hundred and seven obese individuals, defined as a body mass index (BMI) ≤ 26 kg/m2, and 163 lean individuals, defined as a BMI < 26 kg/m2. MEASUREMENTS BMI, blood pressure, serum lipids, alleles of LDLR microsatellite (106 bp, 108 bp and 112 bp). RESULTS There was a significant association between variants of the LDLR microsatellite and obesity, in the overall tested population, due to a contributing effect in females (χ2 = 12.3, P = 0.002), but not in males (χ2 = 0.3, P = 0.87). In females, individuals with the 106 bp allele were more likely to be lean, while individuals with the 112 bp and/or 108 bp alleles tended to be obese. CONCLUSIONS These results suggest that in females, LDLR may play a role in the development of obesity.

Association of a RFLP for the insulin receptor gene, but not insulin, with essential hypertension

Insulin has cardiovascular actions and patients with essential hypertension display insulin resistance. A cross-sectional study of the R1 RFLP of the insulin receptor gene (INSR) was carried out in 67 hypertensive (HT) and 75 normotensive (NT) subjects whose parents had a similar blood pressure status at age ≥50. The frequency of the minor (+) allele was 0.31 in HTs and 0.44 in NTs, and the difference between observed alleles in all subjects in each group was significant (χ2 = 4.8, P<0.05). Allele frequencies of a BglI RFLP of the insulin gene, however, did not differ between the HT and NT groups. The data thus provide evidence in favour of an association of HT with a polymorphism at the INSR locus (19p 13.3-13.2), so implicating this locus, and possibly a genetic variant of the insulin receptor itself, in HT.

Association of HincII RFLP of low density lipoprotein receptor gene with obesity in essential hypertensives

Obese (BMI ≥ 26 kg/m 2; n = 51) and lean (BMI <26 kg/m 2; n = 61) Caucasian patients with severe, familial essential hypertension, were compared with respect to genotype and allele frequencies of a HincII RFLP of the low density lipoprotein receptor gene (LDLR). A similar analysis was performed in obese (n = 28) and lean (n = 68) normotensives. A significant association of the C allele of the T→C variant responsible for this RFLP was seen with obesity (χ 2 = 4.6, P = 0.029) in the hypertensive, but not in the normotensive, group (odds ratio = 3.0 for the CC genotype and 2.7 for CT). Furthermore, BMI tracked with genotypes of this allele in the hypertensives (P = 0.046). No significant genotypic relationship was apparent for plasma lipids. Significant linkage disequilibrium was, moreover, noted between the HincII RFLP and an ApaLI RFLP (χ 2 = 33, P<0.0005) that has previously shown even stronger association with obesity (odds ratio 19.6 for cases homozygous for the susceptibility allele and 15.2 for het-erozygotes). The present study therefore adds to our previous evidence implicating LDLR as a locus for obesity in patients with essential hypertension.

Association and linkage analyses of restriction fragment length polymorphisms for the human renin and antithrombin III genes in essential hypertension

Essential hypertension is a highly hereditable disorder in which genetic influences predominate over environmental factors. The molecular genetic profiles which predispose to essential hypertension are not known. In rats with genetic hypertension, there is some recent evidence pointing to linkage of renin gene alleles with blood pressure. The genes for renin and antithrombin III belong to a conserved synteny group which, in humans, spans the q21.3-32.3 region of chromosome I and, in rats, is linkage group X on chromosome 13. The present study examined the association of particular human renin gene (REN) and antithrombin III gene (AT3) polymorphisms with essential hypertension by comparing the frequency of specific alleles for each of these genes in 50 hypertensive offspring of hypertensive parents and 91 normotensive offspring of normotensive parents. In addition, linkage relationships were examined in hypertensive pedigrees with multiple affected individuals. Alleles of a REN HindIII restriction fragment length polymorphism (RFLP) were detected using a genomic clone, λHR5, to probe Southern blots of HindIII-cut leucocyte DNA, and those for an AT3 Pstl RFLP were detected by phATIII 113 complementary DNA probe. The frequencies of each REN allele in the hypertensive group were 0.76 and 0.24 compared with 0.74 and 0.26 in the normotensive group. For AT3, hypertensive allele frequencies were 0.49 and 0.51 compared with normotensive values of 0.54 and 0.46. These differences were not significant by χ2 analysis (P > 0.2). Linkage analysis of a family (data from 16 family members, 10 of whom were hypertensive), informative for both markers, without an age-of-onset correction, and assuming dominant inheritance of hypertension, complete penetrance and a disease frequency of 20%, did not indicate linkage of REN with hypertension, but gave a positive, although not significant, logarithm of the odds for linkage score of 0.784 at a recombination fraction of 0 for AT3 linkage to hypertension. In conclusion, the present study could find no evidence for an association of a REN HindIII RFLP with essential hypertension or for a linkage of the locus defined by this RFLP in a family segregating for hypertension. In the case of an AT3 Pstl RFLP, although association analysis was negative, linkage analysis suggested possible involvement (odds of 6:1 in favour) of a gene located near the 1q23 locus with hypertension in one informative family.

Closing the case of APOE in multiple sclerosis : no association with disease risk in over 29,000 subjects

Background Single nucleotide polymorphisms (SNPs) rs429358 (ε4) and rs7412 (ε2), both invoking changes in the amino-acid sequence of the apolipoprotein E (APOE) gene, have previously been tested for association with multiple sclerosis (MS) risk. However, none of these studies was sufficiently powered to detect modest effect sizes at acceptable type-I error rates. As both SNPs are only imperfectly captured on commonly used microarray genotyping platforms, their evaluation in the context of genome-wide association studies has been hindered until recently. Methods We genotyped 12 740 subjects hitherto not studied for their APOE status, imputed raw genotype data from 8739 subjects from five independent genome wide association studies datasets using the most recent high-resolution reference panels, and extracted genotype data for 8265 subjects from previous candidate gene assessments. Results Despite sufficient power to detect associations at genome-wide significance thresholds across a range of ORs, our analyses did not support a role of rs429358 or rs7412 on MS susceptibility. This included meta-analyses of the combined data across 13 913 MS cases and 15 831 controls (OR=0.95, p=0.259, and OR 1.07, p=0.0569, for rs429358 and rs7412, respectively). Conclusion Given the large sample size of our analyses, it is unlikely that the two APOE missense SNPs studied here exert any relevant effects on MS susceptibility.

Investigating the association between sun exposure and folate degradation in the human body

This thesis is the first study to investigate the associations between sun exposure and folate degradation in a group of childbearing age women in a high UV environment. It examined whether the degree of sun exposure experienced by women influenced blood folate levels following a period of folic acid supplementation and found a strong significant relationship between increased sun exposure and folate degradation. This relationship has strong implications for public health and the thesis has provided a foundation for further research in this area.

Association between maternal depressive symptoms in the early postnatal period and responsiveness in feeding at child age 2 years

Maternal depression is a known risk factor for poor outcomes for children. Pathways to these poor outcomes relate to reduced maternal responsiveness or sensitivity to the child. Impaired responsiveness potentially impacts the feeding relationship and thus may be a risk factor for inappropriate feeding practices. The aim of this study was to examine the longitudinal relationships between self-reported maternal post-natal depressive symptoms at child age 4 months and feeding practices at child age 2 years in a community sample. Participants were Australian first-time mothers allocated to the control group of the NOURISH randomized controlled trial when infants were 4 months old. Complete data from 211 mothers (of 346 allocated) followed up when their children were 2 years of age (51% girls) were available for analysis. The relationship between Edinburgh Postnatal Depression Scale (EPDS) score (child age 4 months) and child feeding practices (child age 2 years) was tested using hierarchical linear regression analysis adjusted for maternal and child characteristics. Higher EPDS score was associated with less responsive feeding practices at child age 2 years: greater pressure [β = 0.18, 95% confidence interval (CI): 0.04–0.32, P = 0.01], restriction (β = 0.14, 95% CI: 0.001–0.28, P = 0.05), instrumental (β = 0.14, 95% CI: 0.005–0.27, P = 0.04) and emotional (β = 0.15, 95% CI: 0.01–0.29, P = 0.03) feeding practices (ΔR2 values: 0.02–0.03, P < 0.05). This study provides evidence for the proposed link between maternal post-natal depressive symptoms and lower responsiveness in child feeding. These findings suggest that the provision of support to mothers experiencing some levels of depressive symptomatology in the early post-natal period may improve responsiveness in the child feeding relationship.

The association between socioeconomic status and depression in Vietnamese adults : pilot study

This study examined the prevalence of depressive symptoms and elucidated the causal pathway between socioeconomic status and depression in a community in the central region of Vietnam. The study used a combination of qualitative and quantitative research methods. Indepth interviews were applied with two local psychiatric experts and ten residents for qualitative research. A cross sectional survey with structured interview technique was implemented with 100 residents in the pilot quantitative survey. The Center for Epidemiological Studies-Depression Scale (CES-D) was applied to valuate depressive symptoms ( CES-D score over 21) and depression ( CESD core over 25). Ordinary Least Squares Regression following the three steps of Baron and Kenny’s framework was employed for testing mediation models. There was a strong social gradient with respect to depressive symptoms. People with higher education levels reported fewer depressive symptoms (lower CES-D scores). Incomes were also inversely associated with depressive symptoms, but only the ones at the bottom of the quartile income. Low level and unstable individuals in terms of occupation were associated with higher depressive symptoms compared with the highest occupation group. Employment status showed the strongest gradient with respect to its impact on the burden of depressive symptoms compared with other indicators of SES. Findings from this pilot study suggest a pattern on the negative association between socioeconomic status and depression in Vietnamese adults.

Association between xenobiotic gene polymorphisms and non-Hodgkin's lymphoma risk

The last four decades have seen a significant increase in the incidence of non-Hodgkin's lymphoma (NHL) as a possible result of increasing environmental carcinogen exposure, particularly pesticides and solvents. Based on the increasing evidence for an association between carcinogen exposure-related cancer risk and xenobiotic gene polymorphisms, we have undertaken a case-control study of xenobiotic gene polymorphisms in individuals with a diagnosis of NHL. Polymorphisms of six xenobiotic genes (CYP1A1, GSTT1, GSTM1, PON1, NAT1, NAT2) were characterized in 169 individuals with NHL and 205 normal controls using polymerase chain reaction-based methods. Polymorphic frequencies were compared using Fisher's exact tests, and odds ratios for NHL risk were calculated. Among the NHL group, the incidence of GSTT1 null and PON1 BB genotypes were significantly increased compared with controls, 34% vs 14%, and 24% vs 11% respectively. Adjusted odds ratios calculated from multivariate analyses demonstrated that GSTT1 null conferred a fourfold increase in NHL risk (OR = 4.27; 95% CI, 2.40-7.61, P < 0.001) and PON1 BB a 2.9-fold increase (OR = 2.92; 95% CI, 1.49-5.72, P = 0.002). Furthermore, GSTT1 null combined with PON1 BB or GSTM1 null conferred an additional risk of NHL. This is the first time that a PON1 gene polymorphism has been shown to be associated with cancer risk. We conclude that the two polymorphisms, GSTT1 null and PON1 BB, are common genetic traits that pose low individual risk but may be important determinants of overall population NHL risk, particularly among groups exposed to NHL-related carcinogens.

Competing together : assessing the dynamics of team-team and player-team synchrony in professional association football

This study investigated movement synchronization of players within and between teams during competitive association football performance. Cluster phase analysis was introduced as a method to assess synchronies between whole teams and between individual players with their team as a function of time, ball possession and field direction. Measures of dispersion (SD) and regularity (sample entropy – SampEn – and cross sample entropy – Cross-SampEn) were used to quantify the magnitude and structure of synchrony. Large synergistic relations within each professional team sport collective were observed, particularly in the longitudinal direction of the field (0.89 ± 0.12) compared to the lateral direction (0.73 ± 0.16, p < .01). The coupling between the group measures of the two teams also revealed that changes in the synchrony of each team were intimately related (Cross-SampEn values of 0.02 ± 0.01). Interestingly, ball possession did not influence team synchronization levels. In player–team synchronization, individuals tended to be coordinated under near in-phase modes with team behavior (mean ranges between −7 and 5° of relative phase). The magnitudes of variations were low, but more irregular in time, for the longitudinal (SD: 18 ± 3°; SampEn: 0.07 ± 0.01), compared to the lateral direction (SD: 28 ± 5°; SampEn: 0.06 ± 0.01, p < .05) on-field. Increases in regularity were also observed between the first (SampEn: 0.07 ± 0.01) and second half (SampEn: 0.06 ± 0.01, p < .05) of the observed competitive game. Findings suggest that the method of analysis introduced in the current study may offer a suitable tool for examining team’s synchronization behaviors and the mutual influence of each team’s cohesiveness in competing social collectives.

The association of early life supplemental nutrition with lean body mass and grip strength in adulthood : evidence from APCAPS

In the present study, we examined the associations of early nutrition with adult lean body mass (LBM) and muscle strength in a birth cohort that was established to assess the long-term impact of a nutrition program. Participants (n = 1,446, 32% female) were born near Hyderabad, India, in 29 villages from 1987 to 1990, during which time only intervention villages (n = 15) had a government program that offered balanced protein-calorie supplementation to pregnant women and children. Participants’ LBM and appendicular skeletal muscle mass were measured using dual energy x-ray absorptiometry; grip strength and information on lifestyle indicators, including diet and physical activity level, were also obtained. Ages (mean = 20.3 years) and body mass indexes (weight (kg)/height (m)2; mean = 19.5) of participants in 2 groups were similar. Current dietary energy intake was higher in the intervention group. Unadjusted LBM and grip strength were similar in 2 groups. After adjustment for potential confounders, the intervention group had lower LBM (β = −0.75; P = 0.03), appendicular skeletal muscle mass, and grip strength than did controls, but these differences were small in magnitude (<0.1 standard deviation). Multivariable regression analyses showed that current socioeconomic position, energy intake, and physical activity level had a positive association with adult LBM and muscle strength. This study could not detect a “programming” effect of early nutrition supplementation on adult LBM and muscle strength.

A novel process of group-oriented question reduction for rule-based recommendation websites

Several websites utilise a rule-base recommendation system, which generates choices based on a series of questionnaires, for recommending products to users. This approach has a high risk of customer attrition and the bottleneck is the questionnaire set. If the questioning process is too long, complex or tedious; users are most likely to quit the questionnaire before a product is recommended to them. If the questioning process is short; the user intensions cannot be gathered. The commonly used feature selection methods do not provide a satisfactory solution. We propose a novel process combining clustering, decisions tree and association rule mining for a group-oriented question reduction process. The question set is reduced according to common properties that are shared by a specific group of users. When applied on a real-world website, the proposed combined method outperforms the methods where the reduction of question is done only by using association rule mining or only by observing distribution within the group.

Head and neck squamous-cell cancer and its association with polymorphic enzymes of xenobiotic metabolism and repair

Tobacco smoking, alcohol drinking, and occupational exposures to polycyclic aromatic hydrocarbons are the major proven risk factors for human head and neck squamous-cell cancer (HNSCC). Major research focus on gene-environment interactions concerning HNSCC has been on genes encoding enzymes of metabolism for tobacco smoke constituents and repair enzymes. To investigate the role of genetically determined individual predispositions in enzymes of xenobiotic metabolism and in repair enzymes under the exogenous risk factor tobacco smoke in the carcinogenesis of HNSCC, we conducted a case-control study on 312 cases and 300 noncancer controls. We focused on the impact of 22 sequence variations in CYP1A1, CYP1B1, CYP2E1, ERCC2/XPD, GSTM1, GSTP1, GSTT1, NAT2, NQO1, and XRCC1. To assess relevant main and interactive effects of polymorphic genes on the susceptibility to HNSCC we used statistical models such as logic regression and a Bayesian version of logic regression. In subgroup analysis of nonsmokers, main effects in ERCC2 (Lys751Gln) C/C genotype and combined ERCC2 (Arg156Arg) C/A and A/A genotypes were predominant. When stratifying for smokers, the data revealed main effects on combined CYP1B1 (Leu432Val) C/G and G/G genotypes, followed by CYP1B1 (Leu432Val) G/G genotype and CYP2E1 (-70G>T) G/T genotype. When fitting logistic regression models including relevant main effects and interactions in smokers, we found relevant associations of CYP1B1 (Leu432Val) C/G genotype and CYP2E1 (-70G>T) G/T genotype (OR, 10.84; 95% CI, 1.64-71.53) as well as CYP1B1 (Leu432Val) G/G genotype and GSTM1 null/null genotype (OR, 11.79; 95% CI, 2.18-63.77) with HNSCC. The findings underline the relevance of genotypes of polymorphic CYP1B1 combined with exposures to tobacco smoke.

The influence of families on early adolescent school connectedness : evidence that this association varies with adolescent involvement in peer drinking networks

School connectedness is central to the long term well-being of adolescents, and high quality parent-child relationships facilitate school connectedness. This study examined the extent to which family relationship quality is associated with the school connectedness of pre- and early teenagers, and how this association varies with adolescent involvement in peer drinking networks. The sample consisted of 7,372 10-14 year olds recruited from 231 schools in 30 Australian communities. Participants completed the Communities that Care youth survey. A multi-level model of school connectedness was used, with a random term for school-level variation. Key independent variables included family relationship quality, peer drinking networks, and school grade. Control variables included child gender, sensation seeking, depression, child alcohol use, parent education, and language spoken at home. For grade 6 students, the association of family relationship quality and school connectedness was lower when peer drinking networks were present, and this effect was nonsignificant for older (grade 8) students. Post hoc analyses indicated that the effect for family relationship quality on school connectedness was nonsignificant when adolescents in grade 6 reported that the majority of friends consumed alcohol. The results point to the importance of familyschool partnerships in early intervention and prevention.