PMC:4195273 / 79208-83803 JSONTXT

{"project":"TEST0","denotations":[{"id":"25352770-223-231-357872","span":{"begin":408,"end":412},"obj":"[\"9806554\"]"},{"id":"25352770-233-241-357873","span":{"begin":813,"end":817},"obj":"[\"10905499\"]"},{"id":"25352770-233-241-357874","span":{"begin":1278,"end":1282},"obj":"[\"11522684\"]"},{"id":"25352770-233-241-357875","span":{"begin":1811,"end":1815},"obj":"[\"11791158\"]"},{"id":"25352770-235-243-357876","span":{"begin":2049,"end":2053},"obj":"[\"15823203\"]"},{"id":"25352770-232-240-357877","span":{"begin":2260,"end":2264},"obj":"[\"15823203\"]"},{"id":"25352770-235-243-357878","span":{"begin":2525,"end":2529},"obj":"[\"15823203\"]"},{"id":"25352770-227-235-357879","span":{"begin":2933,"end":2937},"obj":"[\"15823203\"]"},{"id":"25352770-229-237-357880","span":{"begin":3283,"end":3287},"obj":"[\"17008116\"]"},{"id":"25352770-230-238-357881","span":{"begin":3776,"end":3780},"obj":"[\"20151954\"]"}],"text":"Table 3 Examples of human studies demonstrating the association between genetic variations in the CART gene and the development of obesity.\nPublication Genetic association study Ethnicity (sample size) Body weight (sample size) Genetic variation/susceptibility locus Occurrence Feeding behavior and body weight alterations Biochemical alteration Energy and glucose homeostasis\nHager et al., 1998 Genome-wide scan for human obesity-susceptibility loci using model-free multipoint linkage analysis French Caucasian (514) Overweight (72), obese (107), morbidly obese (196), and non-obese controls (139) Chromosomal locus 5q13.2 (CART gene) Higher allele frequencies in overweight and obese sibpairs N/A Linkage with ↑ serum leptin levels ↑ Fasting glucose and insulin levels\nChallis et al., 2000 Mutational analysis and population genetics British Caucasian (902) Morbidly obese (91) and non-obese (811) 1475A\u003eG SNP (3′-UTR of exon 3) NSD in allele frequency between obese and control subjects Potential link to early-onset obesity; ↓ waist-to-hip ratio in male heterozygotes Potential interference with fat distribution and contribution to dyslipidaemia ↓ Fasting plasma insulin and fasting triglycerides in male heterozygotes\ndel Giudice et al., 2001 Single-strand conformation polymorphism and automatic sequencing Italian (230) Obese (130) and non-obese controls (100) Leu34Phe missense mutation in pro-CART (729G\u003eC in exon 2) A large family of obese subjects across three generations Hyperphagia and severe early-onset obesity even when heterozygous for allele Altered post-translational processing; intracellular missorting of proCART; bioactive CART deficiency in the serum; ↑ serum leptin levels ↓ Resting metabolic rates; linked to type II diabetes\nYamada et al., 2002 Single-strand conformation polymorphism and direct sequencing Japanese (558) Overweight and obese (528), non-obese controls (30) 6 polymorphic sites at 5′-flanking region, e.g., −156A\u003eG [corresponds to −175A\u003eG (Guerardel et al., 2005)], −929G\u003eC Higher allele frequencies in obese subjects than controls ↑ Genetic predisposition to obesity when in linkage disequliibrium N/A Potential association with type II diabetes\nGuerardel et al., 2005 Sequence variability screen and haplotype analysis French Caucasian (660) Morbidly obese (292) and non-obese controls (368) 1475A\u003eG SNP (3′-UTR of exon 3) Higher allele frequencies in morbidly obese subjects than controls N/A N/A N/A\nGuerardel et al., 2005 Sequence variability screen and haplotype analysis French Caucasian (989) Morbidly obese (621) and non-obese controls (368) 5′ SNPs: −3608T\u003eC, −3607C\u003eT, −1702C\u003eT, −175A\u003eG; 3′UTR SNP: ΔA1457 Higher allele frequencies in morbidly obese subjects than controls; association enhanced with the SNP haplotype structure 3608T\u003eC (or 175A\u003eG) and −1702C\u003eT, combined to ΔA1457 N/A N/A N/A\nGuerardel et al., 2005 Sequence variability screen and haplotype analysis French (2340) and Swiss (385) Caucasian Moderately obese (619), morbidly obese (1006) and non-obese controls (1100) −3608T\u003eC SNP (promoter region) Higher allele frequencies ↑ Genetic predisposition to obesity Potential modulation of nuclear protein binding affinity N/A\nVasseur et al., 2007 Sequence variability screen and haplotype analysis French Caucasian (840) General population sample 5′ SNPs: −3608T\u003eC, −1702C\u003eT, −175A\u003eG (promoter region) NSD in allele frequency between subjects with different BMI; strong linkage disequilibrium between the SNPs, haplotypic effect attributed to −3608T\u003eC N/A ↓ Plasma LDL-cholesterol level and LDL/HDL ratio; potential protection against atherogenesis Potential association with lipid metabolism and atherogenicity\nRigoli et al., 2010 Family-based association methods Italian (320) Overweight (103), obese (30) and non-obese controls (187) 1475A\u003eG SNP (3′-UTR of exon 3) Higher allele frequencies in overweight (0.07) and obese (0.08) children compared to non-obese unrelated controls (children and/or adults) (0.02); preferential transmission of 1475G allele from heterozygous parents to overweight and obese offspring Early-onset obesity N/A N/A\nWith slight variation between different studies, body weight is categorized according to the body mass index (BMI): non-obese (\u003c25 kg/m2), overweight (25–30 kg/m2), moderately obese (30–40 kg/m2), morbidly obese (\u003e40 kg/m2). LDL, low-density lipoprotein; HDL, high-density lipoprotein; NSD, no significant difference; SNP, single nucleotide polymorphism; UTR, untranslated region; Δ, deletion."}

{"project":"0_colil","denotations":[{"id":"25352770-9806554-357872","span":{"begin":408,"end":412},"obj":"9806554"},{"id":"25352770-10905499-357873","span":{"begin":813,"end":817},"obj":"10905499"},{"id":"25352770-11522684-357874","span":{"begin":1278,"end":1282},"obj":"11522684"},{"id":"25352770-11791158-357875","span":{"begin":1811,"end":1815},"obj":"11791158"},{"id":"25352770-15823203-357876","span":{"begin":2049,"end":2053},"obj":"15823203"},{"id":"25352770-15823203-357877","span":{"begin":2260,"end":2264},"obj":"15823203"},{"id":"25352770-15823203-357878","span":{"begin":2525,"end":2529},"obj":"15823203"},{"id":"25352770-15823203-357879","span":{"begin":2933,"end":2937},"obj":"15823203"},{"id":"25352770-17008116-357880","span":{"begin":3283,"end":3287},"obj":"17008116"},{"id":"25352770-20151954-357881","span":{"begin":3776,"end":3780},"obj":"20151954"}],"text":"Table 3 Examples of human studies demonstrating the association between genetic variations in the CART gene and the development of obesity.\nPublication Genetic association study Ethnicity (sample size) Body weight (sample size) Genetic variation/susceptibility locus Occurrence Feeding behavior and body weight alterations Biochemical alteration Energy and glucose homeostasis\nHager et al., 1998 Genome-wide scan for human obesity-susceptibility loci using model-free multipoint linkage analysis French Caucasian (514) Overweight (72), obese (107), morbidly obese (196), and non-obese controls (139) Chromosomal locus 5q13.2 (CART gene) Higher allele frequencies in overweight and obese sibpairs N/A Linkage with ↑ serum leptin levels ↑ Fasting glucose and insulin levels\nChallis et al., 2000 Mutational analysis and population genetics British Caucasian (902) Morbidly obese (91) and non-obese (811) 1475A\u003eG SNP (3′-UTR of exon 3) NSD in allele frequency between obese and control subjects Potential link to early-onset obesity; ↓ waist-to-hip ratio in male heterozygotes Potential interference with fat distribution and contribution to dyslipidaemia ↓ Fasting plasma insulin and fasting triglycerides in male heterozygotes\ndel Giudice et al., 2001 Single-strand conformation polymorphism and automatic sequencing Italian (230) Obese (130) and non-obese controls (100) Leu34Phe missense mutation in pro-CART (729G\u003eC in exon 2) A large family of obese subjects across three generations Hyperphagia and severe early-onset obesity even when heterozygous for allele Altered post-translational processing; intracellular missorting of proCART; bioactive CART deficiency in the serum; ↑ serum leptin levels ↓ Resting metabolic rates; linked to type II diabetes\nYamada et al., 2002 Single-strand conformation polymorphism and direct sequencing Japanese (558) Overweight and obese (528), non-obese controls (30) 6 polymorphic sites at 5′-flanking region, e.g., −156A\u003eG [corresponds to −175A\u003eG (Guerardel et al., 2005)], −929G\u003eC Higher allele frequencies in obese subjects than controls ↑ Genetic predisposition to obesity when in linkage disequliibrium N/A Potential association with type II diabetes\nGuerardel et al., 2005 Sequence variability screen and haplotype analysis French Caucasian (660) Morbidly obese (292) and non-obese controls (368) 1475A\u003eG SNP (3′-UTR of exon 3) Higher allele frequencies in morbidly obese subjects than controls N/A N/A N/A\nGuerardel et al., 2005 Sequence variability screen and haplotype analysis French Caucasian (989) Morbidly obese (621) and non-obese controls (368) 5′ SNPs: −3608T\u003eC, −3607C\u003eT, −1702C\u003eT, −175A\u003eG; 3′UTR SNP: ΔA1457 Higher allele frequencies in morbidly obese subjects than controls; association enhanced with the SNP haplotype structure 3608T\u003eC (or 175A\u003eG) and −1702C\u003eT, combined to ΔA1457 N/A N/A N/A\nGuerardel et al., 2005 Sequence variability screen and haplotype analysis French (2340) and Swiss (385) Caucasian Moderately obese (619), morbidly obese (1006) and non-obese controls (1100) −3608T\u003eC SNP (promoter region) Higher allele frequencies ↑ Genetic predisposition to obesity Potential modulation of nuclear protein binding affinity N/A\nVasseur et al., 2007 Sequence variability screen and haplotype analysis French Caucasian (840) General population sample 5′ SNPs: −3608T\u003eC, −1702C\u003eT, −175A\u003eG (promoter region) NSD in allele frequency between subjects with different BMI; strong linkage disequilibrium between the SNPs, haplotypic effect attributed to −3608T\u003eC N/A ↓ Plasma LDL-cholesterol level and LDL/HDL ratio; potential protection against atherogenesis Potential association with lipid metabolism and atherogenicity\nRigoli et al., 2010 Family-based association methods Italian (320) Overweight (103), obese (30) and non-obese controls (187) 1475A\u003eG SNP (3′-UTR of exon 3) Higher allele frequencies in overweight (0.07) and obese (0.08) children compared to non-obese unrelated controls (children and/or adults) (0.02); preferential transmission of 1475G allele from heterozygous parents to overweight and obese offspring Early-onset obesity N/A N/A\nWith slight variation between different studies, body weight is categorized according to the body mass index (BMI): non-obese (\u003c25 kg/m2), overweight (25–30 kg/m2), moderately obese (30–40 kg/m2), morbidly obese (\u003e40 kg/m2). LDL, low-density lipoprotein; HDL, high-density lipoprotein; NSD, no significant difference; SNP, single nucleotide polymorphism; UTR, untranslated region; Δ, deletion."}

{"project":"2_test","denotations":[{"id":"25352770-9806554-38284861","span":{"begin":408,"end":412},"obj":"9806554"},{"id":"25352770-10905499-38284862","span":{"begin":813,"end":817},"obj":"10905499"},{"id":"25352770-11522684-38284863","span":{"begin":1278,"end":1282},"obj":"11522684"},{"id":"25352770-11791158-38284864","span":{"begin":1811,"end":1815},"obj":"11791158"},{"id":"25352770-15823203-38284865","span":{"begin":2049,"end":2053},"obj":"15823203"},{"id":"25352770-15823203-38284866","span":{"begin":2260,"end":2264},"obj":"15823203"},{"id":"25352770-15823203-38284867","span":{"begin":2525,"end":2529},"obj":"15823203"},{"id":"25352770-15823203-38284868","span":{"begin":2933,"end":2937},"obj":"15823203"},{"id":"25352770-17008116-38284869","span":{"begin":3283,"end":3287},"obj":"17008116"},{"id":"25352770-20151954-38284870","span":{"begin":3776,"end":3780},"obj":"20151954"}],"text":"Table 3 Examples of human studies demonstrating the association between genetic variations in the CART gene and the development of obesity.\nPublication Genetic association study Ethnicity (sample size) Body weight (sample size) Genetic variation/susceptibility locus Occurrence Feeding behavior and body weight alterations Biochemical alteration Energy and glucose homeostasis\nHager et al., 1998 Genome-wide scan for human obesity-susceptibility loci using model-free multipoint linkage analysis French Caucasian (514) Overweight (72), obese (107), morbidly obese (196), and non-obese controls (139) Chromosomal locus 5q13.2 (CART gene) Higher allele frequencies in overweight and obese sibpairs N/A Linkage with ↑ serum leptin levels ↑ Fasting glucose and insulin levels\nChallis et al., 2000 Mutational analysis and population genetics British Caucasian (902) Morbidly obese (91) and non-obese (811) 1475A\u003eG SNP (3′-UTR of exon 3) NSD in allele frequency between obese and control subjects Potential link to early-onset obesity; ↓ waist-to-hip ratio in male heterozygotes Potential interference with fat distribution and contribution to dyslipidaemia ↓ Fasting plasma insulin and fasting triglycerides in male heterozygotes\ndel Giudice et al., 2001 Single-strand conformation polymorphism and automatic sequencing Italian (230) Obese (130) and non-obese controls (100) Leu34Phe missense mutation in pro-CART (729G\u003eC in exon 2) A large family of obese subjects across three generations Hyperphagia and severe early-onset obesity even when heterozygous for allele Altered post-translational processing; intracellular missorting of proCART; bioactive CART deficiency in the serum; ↑ serum leptin levels ↓ Resting metabolic rates; linked to type II diabetes\nYamada et al., 2002 Single-strand conformation polymorphism and direct sequencing Japanese (558) Overweight and obese (528), non-obese controls (30) 6 polymorphic sites at 5′-flanking region, e.g., −156A\u003eG [corresponds to −175A\u003eG (Guerardel et al., 2005)], −929G\u003eC Higher allele frequencies in obese subjects than controls ↑ Genetic predisposition to obesity when in linkage disequliibrium N/A Potential association with type II diabetes\nGuerardel et al., 2005 Sequence variability screen and haplotype analysis French Caucasian (660) Morbidly obese (292) and non-obese controls (368) 1475A\u003eG SNP (3′-UTR of exon 3) Higher allele frequencies in morbidly obese subjects than controls N/A N/A N/A\nGuerardel et al., 2005 Sequence variability screen and haplotype analysis French Caucasian (989) Morbidly obese (621) and non-obese controls (368) 5′ SNPs: −3608T\u003eC, −3607C\u003eT, −1702C\u003eT, −175A\u003eG; 3′UTR SNP: ΔA1457 Higher allele frequencies in morbidly obese subjects than controls; association enhanced with the SNP haplotype structure 3608T\u003eC (or 175A\u003eG) and −1702C\u003eT, combined to ΔA1457 N/A N/A N/A\nGuerardel et al., 2005 Sequence variability screen and haplotype analysis French (2340) and Swiss (385) Caucasian Moderately obese (619), morbidly obese (1006) and non-obese controls (1100) −3608T\u003eC SNP (promoter region) Higher allele frequencies ↑ Genetic predisposition to obesity Potential modulation of nuclear protein binding affinity N/A\nVasseur et al., 2007 Sequence variability screen and haplotype analysis French Caucasian (840) General population sample 5′ SNPs: −3608T\u003eC, −1702C\u003eT, −175A\u003eG (promoter region) NSD in allele frequency between subjects with different BMI; strong linkage disequilibrium between the SNPs, haplotypic effect attributed to −3608T\u003eC N/A ↓ Plasma LDL-cholesterol level and LDL/HDL ratio; potential protection against atherogenesis Potential association with lipid metabolism and atherogenicity\nRigoli et al., 2010 Family-based association methods Italian (320) Overweight (103), obese (30) and non-obese controls (187) 1475A\u003eG SNP (3′-UTR of exon 3) Higher allele frequencies in overweight (0.07) and obese (0.08) children compared to non-obese unrelated controls (children and/or adults) (0.02); preferential transmission of 1475G allele from heterozygous parents to overweight and obese offspring Early-onset obesity N/A N/A\nWith slight variation between different studies, body weight is categorized according to the body mass index (BMI): non-obese (\u003c25 kg/m2), overweight (25–30 kg/m2), moderately obese (30–40 kg/m2), morbidly obese (\u003e40 kg/m2). LDL, low-density lipoprotein; HDL, high-density lipoprotein; NSD, no significant difference; SNP, single nucleotide polymorphism; UTR, untranslated region; Δ, deletion."}