Heritability and genetic etiology of habitual physical activity: a twin study with objective measures.

Twin studies with objective measurements suggest habitual physical activity (HPA) are modestly to highly heritable, depending on age. We aimed to confirm or refute this finding and identify relevant genetic variants using a candidate gene approach. HPA was measured for 14 days with a validated triaxial accelerometer (Tracmor) in two populations: (1) 28 monozygotic and 24 dizygotic same-sex twin pairs (aged 22 ± 5 years, BMI 21.8 ± 3.4 kg/m(2), 21 male, 31 female pairs); (2) 52 and 65 unrelated men and women (aged 21 ± 2 years, BMI 22.0 ± 2.5 kg/m(2)). Single nucleotide polymorphisms (SNPs) in PPARD, PPARGC1A, NRF1 and MTOR were considered candidates. Association analyses were performed for both groups separately followed by meta-analysis. Structural equation modeling shows significant familiality for HPA, consistent with a role for additive genetic factors (heritability 57 %, 95 % CI 32-74 %, AE model) or common environmental factors (47 %, 95 % CI 23-65 %, CE model). A moderate heritability was observed for the time spent on low- and high-intensity physical activity (P ≤ 0.05), but could not be confirmed for the time spent on moderate-intensity physical activity. For PPARD, each additional effect allele was inversely associated with HPA (P ≤ 0.01; rs2076168 allele C) or tended to be associated with HPA (P ≤ 0.05; rs2267668 allele G). Linkage disequilibrium existed between those two SNPs (alleles A/G and A/C, respectively) and meta-analysis showed that carriers of the AA GC haplotype were less physically active than carriers of the AA AA and AA AC haplotypes combined (P = 0.017). For PPARGC1A, carriers of AA in rs8192678 spent more time on high-intensity physical activity than GG carriers (P = 0.001). No associations were observed with SNPs in NRF1 and MTOR. In conclusion, HPA may be modestly heritable, which is confirmed by an association with variants in PPARD.

Factor VII, blood lipids and fat intake: gene-nutrient interaction and risk of coronary heart disease with the factor VII R353Q polymorphism.

BACKGROUND: The relation between dietary fat, blood lipids, plasma factor VII coagulant activity (FVIIc) and risk of coronary heart disease (CHD) according to the R353Q polymorphism in the factor VII gene was assessed. METHODS: Cross-sectional study of 15,073 individuals participating in the European Prospective Investigation of Cancer (EPIC) Norfolk, 7433 of which had FVIIc available. Nested case-control study of 985 CHD cases and 2009 matched controls. RESULTS: FVIIc was significantly associated with total fat intake in females, especially in the RR homozygotes (standardized beta=0.24; 95% confidence interval (95% CI) 0.08-0.40; P<0.01), but there were no associations with intakes of saturated, monounsaturated or polyunsaturated fatty acids according to genotype and no associations in males. FVIIc was significantly positively associated with total cholesterol (P<0.01) and with triacylglycerol (P<0.001) in both genders, with an interaction according to genotype for triacylglycerol in males: beta Q allele carriers 0.26 (95% CI 0.18-0.34), beta RR homozygotes 0.16 (95% CI 0.12-0.20) (Z interaction=-2.24; P<0.05). There was no effect of genotype on the odds ratio (OR) for incident CHD: OR 0.89 for Q allele carriers compared with RR homozygotes (95% CI 0.77-1.02) in 985 cases and 2009 matched controls. CONCLUSION: These results show a strong association between dietary fat intake and FVIIc in women, and between serum triacylglycerol and cholesterol and FVIIc levels in both genders. The R353Q genotype only marginally affected modulation of FVIIc by dietary fat. The association between triacylglycerol and FVIIc was significantly stronger in males carrying the Q allele than in those with the RR genotype.

Urinary sucrose and fructose as biomarkers of sugar consumption: comparison of normal weight and obese volunteers.

Using urinary sugars as a biomarker of consumption, we have previously shown that obese people consume significantly more sugars than individuals of normal weight. However, there is concern that recovery of this biomarker may differ between normal weight and obese individuals. A total of 19 subjects, divided into two groups according to their body mass index (BMI) (normal weight BMI < or = 25 kg/m(2), n=10; obese BMI > or = 30 kg/m(2), n=9), participated in a randomized crossover dietary intervention study of three diets providing 13, 30 and 50% of energy from sugars for 4 days each while living in a volunteer suite. The mean urinary sucrose and fructose excretions in 24-h urine increased with increasing sugar consumption over the three dietary periods in both BMI groups and were significantly different between the diets (P < 0.01). There was no significant interaction effect of BMI class on the mean urinary excretions of these sugars with different sugar intakes, either as absolute values or expressed as a percentage of total sugar intake. In conclusion, BMI does not affect the validity of sucrose and fructose excretions in 24-h urine collections used as biomarkers to estimate total sugar consumption.

PPARgamma activity in subcutaneous abdominal fat tissue and fat mass gain during short-term overfeeding.

OBJECTIVE: As the peroxisome proliferator-activated receptor gamma (PPARgamma) plays a central role in fat mass regulation, we investigated whether initial subcutaneous PPARgamma activity is related to fat mass generation during overfeeding. SUBJECTS: Fourteen healthy female subjects (age 25 +/- 4 years, BMI 22.1 +/- 2.3 kg/m2). DESIGN AND MEASUREMENTS: Subjects were overfed with a diet supplying 50% more energy than baseline energy requirements for 14 days. Fasting blood samples were analyzed for leptin, insulin and glucose. Fasting subcutaneous abdominal fat biopsies were obtained for analysis of PPARgamma1, PPARgamma2, aP2 and UCP2 mRNAs. RESULTS: Initial PPARgamma1 and 2, aP2 and UCP2 mRNAs were not related to fat gain (P > 0.12). However, PPARgamma1, PPARgamma2 and aP2 mRNA changes were positively related to changes in plasma leptin (P < 0.05) and, except aP2 (P = 0.06), to fat gain (P < 0.05). PPARgamma and aP2 mRNA changes were positively related (P<0.01), indicating that PPARgamma mRNA levels reflected PPARgamma activity. CONCLUSION: These data suggest that the ability to increase PPARgamma activity might be involved in the susceptibility to gain weight during a positive energy balance.