Genetic variation in a member of the laminin gene family affects variation in body composition in Drosophila and humans

<p>Abstract</p> <p>Background</p> <p>The objective of the present study was to map candidate loci influencing naturally occurring variation in triacylglycerol (TAG) storage using quantitative complementation procedures in <it>Drosophila melanogaster</it>. Based on our results from <it>Drosophila</it>, we performed a human population-based association study to investigate the effect of natural variation in <it>LAMA5 </it>gene on body composition in humans.</p> <p>Results</p> <p>We identified four candidate genes that contributed to differences in TAG storage between two strains of <it>D. melanogaster</it>, including <it>Laminin A </it>(<it>LanA</it>), which is a member of the α subfamily of laminin chains. We confirmed the effects of this gene using a viable <it>LanA </it>mutant and showed that female flies homozygous for the mutation had significantly lower TAG storage, body weight, and total protein content than control flies. <it>Drosophila LanA </it>is closely related to human <it>LAMA5 </it>gene, which maps to the well-replicated obesity-linkage region on chromosome 20q13.2-q13.3. We tested for association between three common single nucleotide polymorphisms (SNPs) in the human <it>LAMA5 </it>gene and variation in body composition and lipid profile traits in a cohort of unrelated women of European American (EA) and African American (AA) descent. In both ethnic groups, we found that SNP rs659822 was associated with weight (EA: <it>P </it>= 0.008; AA: <it>P </it>= 0.05) and lean mass (EA: <it>P= </it>0.003; AA: <it>P </it>= 0.03). We also found this SNP to be associated with height (<it>P </it>= 0.01), total fat mass (<it>P </it>= 0.01), and HDL-cholesterol (<it>P </it>= 0.003) but only in EA women. Finally, significant associations of SNP rs944895 with serum TAG levels (<it>P </it>= 0.02) and HDL-cholesterol (<it>P </it>= 0.03) were observed in AA women.</p> <p>Conclusion</p> <p>Our results suggest an evolutionarily conserved role of a member of the laminin gene family in contributing to variation in weight and body composition.</p

The uncoupling protein 1 gene, UCP1, is expressed in mammalian islet cells and associated with acute insulin response to glucose in African American families from the IRAS Family Study

BACKGROUND: Variants of uncoupling protein genes UCP1 and UCP2 have been associated with a range of traits. We wished to evaluate contributions of known UCP1 and UCP2 variants to metabolic traits in the Insulin Resistance and Atherosclerosis (IRAS) Family Study. METHODS: We genotyped five promoter or coding single nucleotide polymorphisms (SNPs) in 239 African American (AA) participants and 583 Hispanic participants from San Antonio (SA) and San Luis Valley. Generalized estimating equations using a sandwich estimator of the variance and exchangeable correlation to account for familial correlation were computed for the test of genotypic association, and dominant, additive and recessive models. Tests were adjusted for age, gender and BMI (glucose homeostasis and lipid traits), or age and gender (obesity traits), and empirical P-values estimated using a gene dropping approach. RESULTS: UCP1 A-3826G was associated with AIR(g )in AA (P = 0.006) and approached significance in Hispanic families (P = 0.054); and with HDL-C levels in SA families (P = 0.0004). Although UCP1 expression is reported to be restricted to adipose tissue, RT-PCR indicated that UCP1 is expressed in human pancreas and MIN-6 cells, and immunohistochemistry demonstrated co-localization of UCP1 protein with insulin in human islets. UCP2 A55V was associated with waist circumference (P = 0.045) in AA, and BMI in SA (P = 0.018); and UCP2 G-866A with waist-to-hip ratio in AA (P = 0.016). CONCLUSION: This study suggests a functional variant of UCP1 contributes to the variance of AIR(g )in an AA population; the plausibility of this unexpected association is supported by the novel finding that UCP1 is expressed in islets

Prevalência de sobrepeso e obesidade em crianças e adolescentes de diferentes condições socioeconômicas Prevalence of overweight and obesity in children and adolescents of different socioeconomic conditions

OBJETIVOS: comparar as prevalências de sobrepeso e obesidade em um grupo de pré-escolares, escolares e adolescentes de diferentes condições socioeconômicas na cidade do Recife. MÉTODOS: estudo do tipo transversal envolvendo uma amostra de 1616 crianças e adolescentes, escolhida por conveniência. Os indicadores nutricionais foram definidos conforme as recomendações do National Center of Health Statistics 2000, sendo considerado sobrepeso o índice de massa corporal igual ou superior ao percentil 85 e inferior ao percentil 95 e obesidade, o índice de massa corporal igual ou superior ao percentil 95. RESULTADOS: foi identificado sobrepeso em 234 (14,5%) indivíduos e obesidade, em 134 (8,3%). A prevalência de sobrepeso foi maior nos pré-escolares (22,2%), observando-se redução progressiva da freqüência nas faixas etárias de escolar (12,9%) e adolescente (10,8%). Constatou-se fato idêntico quanto à obesidade, detectada em 13,8% dos pré-escolares, 8,2% dos escolares e 4,9% dos adolescentes. O sobrepeso e a obesidade foram mais observados entre crianças e adolescentes de melhor condição socioeconômica. CONCLUSÕES: as prevalências de sobrepeso e obesidade diminuíram à medida que ocorreu aumento da faixa etária. Entre os pré-escolares observou-se prevalência de sobrepeso semelhante, independente das condições socioeconômicas. A prevalência da obesidade foi maior entre escolares de boas condições socioeconômicas e adolescentes de baixa condição socioeconômica.<br>OBJECTIVES: to compare overweight and obesity in preschool children, school children and adolescents belonging to different socioeconomic conditions. METHODS: cross-sectional and based on a 1616 children and adolescents sample. Nutritional indicators were defined according to the National Center of Health Statistics 2000 recommendations, overweight being BMI equal to or above 85 percentile and below percentile 95; obesity indicator being defined with BMI equal to or above the 95 percentile. RESULTS: overweight was detected in 234 (14.5%) individuals and obesity in 134 (8.3%). Overweight prevalence was higher among preschool children (22.2%), though prevalence reduction was noted in younger school children (12.9%) and adolescents (10.8%). A similar pattern was found for obesity in 13.8% of preschool children, 8.2% of school children, and 4.9% of adolescents. Overweight and obesity were mostly observed among children and adolescents of high income families. CONCLUSIONS: as age increases overweight and obesity diminish. Similar overweight prevalence was detected among preschool children irrespective of socioeconomic conditions. Overweight prevalence was highest among school children with high socioeconomic conditions and adolescents with low socioeconomic conditions

Deprivation and childhood obesity: a cross sectional study of 20 973 children in Plymouth, United Kingdom

OBJECTIVE—To study the association between socioeconomic deprivation and childhood obesity.
DESIGN—Cross sectional study.
SETTING—All state primary schools in Plymouth. Plymouth is a relatively deprived city in the United Kingdom, ranking 338th of 366( )local authorities on the Department of the Environment Index of Local Conditions.
SUBJECTS—20 973 children between the ages of 5 and 14 years, 1994-96.
MAIN OUTCOME MEASURE—Numbers of obese children (body mass index (BMI) above the 98th centile) by quarters of Townsend score.
RESULTS—Plymouth had a rate of childhood obesity two and half times that expected nationally (5% v 2%). The obesity prevalence increased with age, being almost double in the oldest age quarter (boys 6.2%; girls 7.0%), compared with the youngest age quarter. Within Plymouth, there was a significant trend for higher rates of obesity related to increasing deprivation in both boys (p=0.017) and girls (p=0.018). The odds ratio (OR) for childhood obesity (highest-lowest quarter of Townsend scores) had borderline significance in boys (OR 1.29, 95% confidence intervals (CI) 1.00 to 1.65, p=0.049) but was larger and more significant in the girls (OR 1.39, 95% CI 1.08 to 1.80, p=0.011). Unlike boys, the association between obesity in girls and Townsend scores became stronger with age such that in the oldest age quarter (over 11.7 years), girls in the highest quarter of Townsend scores were nearly twice as likely be obese, as compared with the lowest quarter (OR 1.95, 95% CI 1.23 to 3.08, p=0.005). State of pubertal development could not be accounted for as this information was not available.
CONCLUSIONS—This study provides evidence for an association between deprivation and childhood obesity in this English population. The health of children from deprived households is affected by a number of adverse influences. The high prevalence of obesity in these children is yet another factor that could predispose to greater morbidity in adult life.


Keywords: childhood obesity; socioeconomic deprivation; body mass index; Townsend material deprivation scor