Julie A Gilg

St. George's School, Middletown, Rhode Island, United States

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Publications (11)104.05 Total impact

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    ABSTRACT: Recent studies suggest an association between a microsatellite locus (TH01) located in intron 1 of the tyrosine hydroxylase gene (TH) and nicotine dependence. We aimed here to study whether both TH01 and haplotypes of the wider IGF2-INS-TH region influence initiation of regular smoking in current smokers. A total of 3637 individuals from three independent studies (two of adults and one of adolescents) were analysed in relation to the age of first regular smoking (AFRS). Haplotypes and genotypes were obtained for the polymorphisms TH01, IGF2 ApaI, INS HphI and DRD4 VNTR (48 bp)n. Association between IGF2-INS-TH haplotypes and AFRS was tested by a regression model. A genotype-based genetic model assuming additivity was followed in order to estimate the effect of individual loci. Overall, no significant associations were found after correcting for multiple tests. However, an IGF2-INS-TH haplotype (*5) was found to be nominally associated with AFRS at younger ages in adult smokers. Analyses of individual loci points to TH01 as a possible candidate influencing initiation of regular smoking. An AFRS-lowering trend nominally associated with allele 9 in a dosage-dependent manner was identified in both adult cohorts. TH01 did not show association or trend with age of initiation (first puff) either in adolescents or in the adolescents smoking regularly at age 18. This study adds to the genetic evaluation of the associations of TH01 with smoking predisposition. Differences between historical and prospective surveys, different biological pathways and possible functional roles of this microsatellite in smoking initiation are discussed.
    Pharmacogenetics and Genomics 02/2006; 16(1):15-23. · 3.61 Impact Factor
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    ABSTRACT: Smoking is a major cause of death and often initiates in adolescence. Mutations in CYP2A6 slow metabolism of nicotine to cotinine. Haploinsufficiency in adults is associated with lower cigarette consumption, lower cotinine level and higher quit rates. Other genes are also implicated in smoking behaviour. We explored smoking behaviour and cotinine levels in relation to genotypes in adolescents. 1518 subjects from the Ten Towns Heart Health Study were genotyped for CYP2A6 alleles *1A, *1B, *2, *4, *5, *9 and *12 to classify predicted nicotine metabolism rate. DBH(rs77905), MAOA(rs1801291+VNTR), DRD4(VNTR) and 5HT2A(rs6313) were also studied. Smoking status was established by questionnaire and salivary cotinine measurement at 13-15 and 18 years. No significant associations were identified for DBH, MAOA, DRD4 and 5HT2A markers, with smoking status or cotinine level at either age. At age 18, haploinsufficiency (HI) for CYP2A6 was associated with a higher odds of being a current smoker compared with the *1B carriers (WT1B) (OR = 2.23 (1.16, 4.27) for current versus ex); *1A homozygotes (WT1A) were also at slightly higher risk (OR = 1.44 (1.01, 2.06)). Partial haploinsufficiency (PHI) was not associated with being a current smoker. There were no significant associations at age 13-15. PHI and HI were associated with higher cotinine levels amongst smokers at both 13-15 and at 18 years compared with WT1B and WT1A groups. CYP2A6 haploinsufficiency increases likelihood of continuing smoking in teenagers. We hypothesize an explanatory 'occupancy' model to explain why haploinsufficiency results in faster progression to nicotine dependence, but lower subsequent consumption.
    Pharmacogenetics and Genomics 01/2006; 15(12):839-50. · 3.61 Impact Factor
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    ABSTRACT: Atherosclerosis develops from childhood, but the determinants of this preclinical stage remain uncertain. We examined the relations of classic coronary risk factors, adiposity and its associated metabolic disturbances, to arterial distensibility (a marker of early arterial disease) in 13- to 15-year-olds, some of whom had previously been studied at ages 9 to 11 years. Brachial artery distensibility was measured by a noninvasive ultrasound technique in 471 British children in whom measures of adiposity, blood pressure, fasting blood lipids, and insulin had been made. All adiposity measures showed strong graded inverse relationships with distensibility. Inverse associations with distensibility were also observed for insulin resistance (homeostasis model assessment), diastolic pressure, C-reactive protein, and the number of metabolic syndrome components present, which had a graded relation to distensibility. Total and LDL cholesterol levels were also inversely related to distensibility, but less strongly than adiposity; homocysteine had no relation to distensibility. Although the relations of total and LDL cholesterol and diastolic pressure to distensibility had been present at 9 to 11 years of age, those of adiposity and insulin resistance were only apparent at 13 to 15 years. Adiposity and its metabolic consequences are associated with adverse changes in the arterial wall by the teenage years. The graded relation with increasing adiposity was stronger than that for cholesterol and was seen at body mass index levels well below those considered to represent "obesity." This emphasizes the importance of population-based strategies to control adiposity and its metabolic consequences in the young.
    Circulation 10/2005; 112(12):1789-97. · 15.20 Impact Factor
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    ABSTRACT: To examine whether plasma glucose, insulin resistance and markers of adiposity differed between British adolescents of South Asian and European origin. School-based cross-sectional study (1998-2000), in which detailed measurements of adiposity, fasting plasma glucose and serum insulin were made in 90 South Asian and 1248 European pupils (overall 69% response rate). Compared with Europeans, South Asian subjects had higher mean fasting insulin levels (percentage mean difference 17.2%, 95% confidence interval 7.2-26.1%, P = 0.001), a higher mean fasting glucose (mean difference 0.19 mmol/l, 95% confidence interval 0.08-0.29 mmol/l, P = 0.0005) and a higher prevalence of impaired fasting glucose (> or = 6.1 mmol/l) (5.6% vs. 1.5%, odds ratio 3.9, 95% confidence interval 1.4-10.9, P = 0.004). Although South Asian children tended to have slightly higher indices of adiposity than Europeans (other than body mass index), the differences in glucose and insulin levels persisted after adjustment for adiposity and for pubertal status. The predisposition to Type 2 diabetes observed in South Asian adults is apparent before adult life. Establishing the contributions of the childhood and fetal environments and of genetic factors to the development of these ethnic differences is an important priority. Prevention of Type 2 diabetes in British South Asians needs to begin before adult life.
    Diabetic Medicine 09/2005; 22(9):1275-7. · 3.24 Impact Factor
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    ABSTRACT: To examine the associations between a biomarker of overall passive exposure to tobacco smoke (serum cotinine concentration) and risk of coronary heart disease and stroke. Prospective population based study in general practice (the British regional heart study). 4729 men in 18 towns who provided baseline blood samples (for cotinine assay) and a detailed smoking history in 1978-80. Major coronary heart disease and stroke events (fatal and non-fatal) during 20 years of follow up. 2105 men who said they did not smoke and who had cotinine concentrations < 14.1 ng/ml were divided into four equal sized groups on the basis of cotinine concentrations. Relative hazards (95% confidence intervals) for coronary heart disease in the second (0.8-1.4 ng/ml), third (1.5-2.7 ng/ml), and fourth (2.8-14.0 ng/ml) quarters of cotinine concentration compared with the first (> or = 0.7 ng/ml) were 1.45 (1.01 to 2.08), 1.49 (1.03 to 2.14), and 1.57 (1.08 to 2.28), respectively, after adjustment for established risk factors for coronary heart disease. Hazard ratios (for cotinine 0.8-14.0 nu > or = 0.7 ng/ml) were particularly increased during the first (3.73, 1.32 to 10.58) and second five year follow up periods (1.95, 1.09 to 3.48) compared with later periods. There was no consistent association between cotinine concentration and risk of stroke. Studies based on reports of smoking in a partner alone seem to underestimate the risks of exposure to passive smoking. Further prospective studies relating biomarkers of passive smoking to risk of coronary heart disease are needed.
    BMJ (online) 07/2004; 329(7459):200-5. · 17.22 Impact Factor
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    ABSTRACT: To determine whether breast feeding in infancy compared with bottle feeding formula milk is associated with lower mean blood pressure at different ages. Systematic review. Embase, Medline, and Web of Science databases. Studies showing the effects of feeding in infancy on blood pressure at different ages. Pooled mean differences in blood pressure between breast fed infants and those bottle fed formula milk, based on random effects models. The pooled mean difference in systolic blood pressure was -1.10 mm Hg (95% confidence interval -1.79 to -0.42 mm Hg) but with significant heterogeneity between estimates (P < 0.001). The difference was largest in studies of < 300 participants (-2.05 mm Hg, -3.30 to -0.80 mm Hg), intermediate in studies of 300-1000 participants (1.13 mm Hg, -2.53 to 0.27 mm Hg), and smallest in studies of > 1000 participants (-0.16 mm Hg, -0.60 to 0.28 mm Hg). An Egger test but not Begg test was statistically significant for publication bias. The difference was unaltered by adjustment for current size and was independent of age at measurement of blood pressure and year of birth. Diastolic blood pressure was not significantly related to type of feeding in infancy. Selective publication of small studies with positive findings may have exaggerated claims that breast feeding in infancy reduces systolic blood pressure in later life. The results of larger studies suggest that feeding in infancy has at most a modest effect on blood pressure, which is of limited clinical or public health importance.
    BMJ (online) 12/2003; 327(7425):1189-95. · 17.22 Impact Factor
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    ABSTRACT: To examine the relationship between birth weight and blood total cholesterol (TC) and to compare its strength with that of the relationship between current body mass index and TC. 1). Cross-sectional study of adolescents, with retrospective ascertainment of birth weight from birth records or parental recall; 2). systematic review of studies examining the relations between birth weight and cholesterol at all ages. 1). 1532 individuals (92% white, 55% male) in 10 British towns; 2). 28 studies with 32 observations showing the change in TC per 1 kg increase in birth weight-6 in infancy, 14 in adolescents, 12 in adults. In the cross-sectional study, there was a weak inverse relation between birth weight and TC level (-.061 mmol/L fall in TC per kg increase in birth weight, 95% confidence interval -.131 to.008 mmol/L per kg) which was little affected by adjustment for current body size. The difference in TC corresponding to an interquartile range increase in birth weight (-.03 mmol/L) was approximately a quarter of that for an equivalent increase in body mass index (.11 mmol/L). In the systematic review, an inverse association between birth weight and TC of a similar size to that in the cross-sectional study was observed (-.048 mmol/L per kg, 95% confidence interval -.078 to -.018 mmol/L per kg) similar in strength at all ages. The relation of fetal nutrition to TC appears to be weak and is probably of limited public health importance when compared with the effects of childhood obesity.
    PEDIATRICS 06/2003; 111(5 Pt 1):1081-9. · 4.47 Impact Factor
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    ABSTRACT: This population-based cross-sectional study in South London looks at the total homocysteine (tHcy) levels in groups of different ethnic background and the possible role of environmental factors and the 677C-->T genetic polymorphism of the methylenetetrahydrofolate reductase (MTHFR). Fasting plasma tHcy was measured in 1392 men and women, age 40-59 years; 475 were white, 465 of African origin (of whom 180 were West Africans and 280 Caribbeans) and 452 South Asian (of whom 222 were Hindus and 167 Muslims). The homozygous MTHFR TT variant had observed frequencies of 0.10 in whites, 0.01 in people of African origin and 0.02 in South Asians (P<0.001). tHcy levels were 16% (95% CI 8-26) higher amongst TT than CC. tHcy levels were 25% (21-29) higher in men than women. Levels were significantly higher in South Asians than whites (8% [3-13]). Vegetarians had higher levels than non-vegetarians (25% [18-33]). These differences were present after adjustments for age, sex, smoking, body mass index (BMI), MTHFR 677C-->T polymorphism and socio-economic status. Compared with whites (10.0 [9.7-10.3] micromol/l), and allowing for confounders, Hindus had significantly higher levels of tHcy (12.1 [11.6-12.6] micromol/l). This difference was attenuated by the inclusion of vegetarianism in the model (11.3 [10.8-11.9] micromol/l). In contrast Muslims had similar tHcy levels to whites while both West Africans and Caribbeans had slightly lower levels, though differences were not significant. The reported higher levels of tHcy in South Asians are due to high levels amongst Hindus only. They are in part accounted for by their vegetarianism. These differences in tHcy are large enough to be important contributors to the risk of vascular disease and may be preventable by simple targeted population strategies.
    Atherosclerosis 10/2002; 164(1):95-102. · 3.71 Impact Factor
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    ABSTRACT: To examine the influence of infant feeding method on serum total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol. A cross-sectional study of 13- to 16-year-olds and a systematic review of studies (all observational) on the effects of infant feeding on cholesterol in infancy (<1 year), childhood or adolescence (1-16 years), and adulthood (> or =17 years) were conducted using random effects models. Differences are presented as breastfed-bottle-fed. A total of 1532 individuals (92% white; 55% male; mean age: 15.1 years) in 10 British towns were studied, and 37 studies with 52 observations on TC (26 in infancy, 17 in childhood or adolescence, and 9 in adulthood; corresponding figures for LDL were 7, 4, and 6) were reviewed. Mean TC in childhood or adolescence (including the new study) was not related to infant feeding pattern (mean TC difference = 0.00; 95% confidence interval [CI]: -0.07 to 0.07 mmol/L). However, in infancy, mean TC was higher among those breastfed (mean TC difference = 0.64; 95% CI: 0.50-0.79 mmol/L), whereas in adults, mean TC was lower among those breastfed (mean TC difference = -0.18; 95% CI: -0.30 to -0.06 mmol/L). Patterns for LDL were similar to those for TC throughout. Breastfeeding is associated with increased mean TC and LDL levels in infancy but lower levels in adulthood/adult life. These results suggest that breastfeeding may have long-term benefits for cardiovascular health and may have implications for the content of formula feed milks.
    PEDIATRICS 09/2002; 110(3):597-608. · 4.47 Impact Factor
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    ABSTRACT: To examine whether British South Asian children differ in insulin resistance, adiposity, and cardiovascular risk profile from white children. Cross sectional study. Primary schools in 10 British towns. British children aged 8 to 11 years (227 South Asian and 3415 white); 73 South Asian and 1287 white children aged 10 and 11 years provided blood samples (half fasting, half after glucose load). Insulin concentrations, anthropometric measures, established cardiovascular risk factors. Mean ponderal index was lower in South Asian children than in white children (mean difference -0.43 kg/m(3), 95% confidence interval -0.13 kg/m(3) to -0.73 kg/m(3)). Mean waist circumferences and waist:hip ratios were similar. Mean insulin concentrations were higher in South Asian children (percentage difference was 53%, 14% to 106%, after fasting and 54%, 19% to 99%, after glucose load), though glucose concentrations were similar. Mean heart rate and triglyceride and fibrinogen concentrations were higher among South Asian children; serum total, low density lipoprotein, and high density lipoprotein cholesterol concentrations were similar in the two groups. Differences in insulin concentrations remained after adjustment for adiposity and other potential confounders. However, the relations between adiposity and insulin concentrations (particularly fasting insulin) were much stronger among South Asian children than among white children. The tendency to insulin resistance observed in British South Asian adults is apparent in children, in whom it may reflect an increased sensitivity to adiposity. Action to prevent non-insulin dependent diabetes in South Asian adults may need to begin during childhood.
    BMJ (online) 04/2002; 324(7338):635. · 17.22 Impact Factor
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    BMJ Clinical Research 06/2001; 322(7294):1095-6. · 14.09 Impact Factor