Genetic variation and decreased risk for obesity in the Atherosclerosis Risk in Communities Study

Sailors, Mary L; Folsom, Aaron R.; Ballantyne, Christie M.; Hoelscher, Deanna M.; Jackson, Andrew S.; Kao, W. H. Linda; Pankow, James S.; Bray, Molly S.

doi:10.1111/j.1463-1326.2006.00637.x

Cited by 24 publications

(19 citation statements)

References 38 publications

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“…[17][18][19][20][21][22] Because some studies used either small and/or selected samples and the criteria utilized to classify cases and controls differed largely, the relation between this SNP and type 2 diabetes Common SNPs in LEP and LEPR NY Souren et al and/or obesity is still unclear. Our data suggest that the LEP 19G4A SNP may be protective against cardiovascular disease, as G allele carriers have significantly higher HDL cholesterol levels.…”

Section: Discussionmentioning

confidence: 99%

“…In this study we therefore examined the effect of common SNPs in LEP and LEPR on birth weight and adult metabolic risk factors for type 2 diabetes measured in young twins recruited from the East Flanders Prospective Twin Survey (EFPTS). The SNPs studied have previously been associated with type 2 diabetesrelated traits in other populations, [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] and are either nonsynonymous or located in a region that might be of importance in the regulation of gene expression.…”

Section: Introductionmentioning

confidence: 99%

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Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins

et al. 2008

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Objective: Children born small for gestational age are at increased risk of developing type 2 diabetes in adulthood. The satiety signal leptin that regulates food intake and energy expenditure might be a possible molecular link, as umbilical cord leptin levels are positively correlated with birth weight. In the present study, we examined whether common single nucleotide polymorphisms (SNPs) in the leptin (LEP; 19G4A) gene and its receptor (LEPR; Q223R and K109R) are associated with birth weight and adult metabolic risk factors for type 2 diabetes in twins. Design: SNPs were genotyped in 396 monozygotic and 232 dizygotic twins (286 men and 342 women, mean age 25 years) recruited from the East Flanders Prospective Twin Survey. Data were analysed using linear mixed models. Results: The LEPR K109R SNP was associated with birth weight (KK, KR and RR (95% confidence interval, CI): 2511 (2465-2557), 2575 (2516-2635) and 2726 (2606-2845) gram; P additive ¼ 0.001). Also the LEPR Q223R SNP showed a significant association with weight at birth (QQ, QR and RR (95% CI): 2492 (2431-2554), 2545 (2495-2595) and 2655 (2571-2740) gram; P additive ¼ 0.003). Furthermore, an interaction between the LEPR K109R and the Q223R SNP on birth weight was observed (P ¼ 0.014). G allele carriers of the LEP 19G4A SNP had higher high-density lipoprotein (HDL) cholesterol levels compared to 19A homozygotes (GX vs AA (95% CI): 1.62 (1.58-1.66) vs 1.49 (1.40-1.58) mmol l À1 ; P recessive ¼ 0.013). Conclusions: This study indicates that leptin may act as a growth-promoting signal during fetal development, and suggests a possible role for the LEPR in explaining the inverse relationship between birth weight and the development of metabolic diseases in adulthood. Additionally, these results suggest that the LEP 19G4A SNP affect HDL cholesterol levels.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins

et al. 2008

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“…The influence of I/G variant was further demonstrated to be related to gender, even though this variable did not affect the distribution of the LEP I/G genotypes. Accordingly, it has been shown that the association between a LEP variant (A19G) and risk for obesity was restricted to females from the Atherosclerosis Risk in Communities (ARIC) Study (35).…”

Section: Discussionmentioning

confidence: 99%

Relationship between variants of the leptin gene and obesity and metabolic biomarkers in Brazilian individuals

Hinuy¹,

Hirata²,

Sampaio³

et al. 2010

Arq Bras Endocrinol Metab

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Objective:The relationship between variants of the leptin gene (LEP) and obesity and metabolic biomarkers was investigated in Brazilian individuals. Subjects and methods: One-hundred-ten obese (BMI > 30 kg/m 2 ) and 100 non-obese individuals (145 women and 65 men, aged 49 ± 14 years) were randomly selected. Plasma leptin, glycemia, serum lipid measurements and LEP -2548G>A and 3'HVR polymorphisms were analyzed. Results: The LEP -2548GG genotype was associated with a 2.2% and 2.0% increase in BMI (p = 0.009) and plasma leptin (p = 0.031), respectively. 3'HVR I/II (classes I/I+I/II) genotypes contributed with 1.8% of BMI values (p = 0.046). LEP I/G combined genotypes (I/IGG, I/IGA and I/IIGG) were associated with obesity, and increased BMI, waist circumference, leptin and triglycerides (p < 0.05). These relationships were found in women (p < 0.05) but not in men. LEP I/G combined genotypes were not associated with hypertension, hyperglycemia, dyslipidemia and coronary artery disease. Conclusions: LEP I/G combined genotypes are associated with obesity-related metabolic biomarkers and phenotype in a gender-dependent manner. Arq Bras Endocrinol Metab. 2010;54(3):282-8 Keywords Leptin; gene polymorphism; obesity; metabolic biomarkers; plasma leptin rEsUMO Objetivo: A relação entre as variantes do gene da leptina (LEP) e obesidade e biomarcadores metabólicos foi investigada em indivíduos brasileiros. Sujeitos e métodos: Cento e dez indiví-duos obesos (IMC > 30 kg/m 2 ) e 100 não obesos (145 mulheres e 65 homens, idade 49 ± 14 anos) foram selecionados aleatoriamente. Leptina plasmática, glicemia, lípides séricos e polimorfismos LEP -2548G>A e 3'HVR foram analisados. Resultados: O genótipo -2548GG foi associado com aumento de 2,2% e 2,0% no IMC (p = 0,009) e leptina plasmática (p = 0,031), respectivamente, enquanto os genótipos 3´HVR I/II (classes I/I+I/II) contribuíram com 1,8% dos valores de IMC (p = 0,046). Os genótipos combinados LEP I/G (I/IGG, I/IGA e I/IIGG) foram associados com obesidade e IMC aumentado, circunferência abdominal, leptina e triglicérides aumentados (p < 0,05). Essas relações foram encontradas em mulheres (p < 0,05), mas não em homens. Os genótipos LEP I/G combinados não foram associados com hipertensão, hiperglicemia, dislipidemia e doença arterial coronariana. Conclusões: Genótipos combinados LEP I/G são associados com biomarcadores metabólicos e fenótipo de obesidade de forma gênero-dependente. Arq Bras Endocrinol Metab. 2010;54(3):282-8 Descritores Leptina; polimorfismo genético; obesidade; biomarcadores metabólicos; leptina plasmática

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“…The LEPR polymorphisms (Lys 109 Arg, Gln 223 Arg and Lys 656 Asn) have been found to be either associated with [48,49,50] or not have any effect [51] on obesity or its anthropometric phenotype indicators. The LEP 19A→G polymorphism has been associated with obesity and leptin levels [18,52,53], while other studies reported a lack of association [20,54]. LD between the genotyped polymorphism and the causal one is reported to be one of the possible reasons for between-study heterogeneity.…”

Section: Discussionmentioning

confidence: 93%

Association of Cocaine- and Amphetamine-Related Transcript, Leptin and Leptin Receptor Gene Polymorphisms with Anthropometric Obesity Phenotype Indicators in South African Learners

Yako

Fanampe²,

Hassan³

et al. 2011

Lifestyle Genomics

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Background/Aims: Obesity has increased rapidly in South African children and adolescents. Genes involved in appetite regulation have been extensively studied worldwide, but their role in the obesity phenotype in South African Black and mixed-ancestry school adolescents is unknown. Methods: Seven common polymorphisms in LEP, GHRL, CART and LEPR were analysed for genotype and haplotype association with anthropometric obesity phenotype indicators in South African Black and mixed-ancestry adolescent school learners. Results: The CART c.517A→G polymorphism was significantly associated with obesity susceptibility. The LEPR Lys¹⁰⁹Arg G allele was associated with an average reduction of 2.36 kg/m² in body mass index (BMI), 5.66 cm in waist circumference (WC) and 1.61 cm in mid-upper-arm circumference (MUAC). This was confirmed by haplotype analysis. Additionally, a haplotype of the LEP polymorphisms significantly increased BMI, MUAC and hip circumference, while LEPR haplotypes were associated with differences in MUAC. Conclusion: Our findings suggest that c.517A→G and Lys¹⁰⁹Arg contribute to the variation in anthropometric obesity phenotype indicators observed among Black African and mixed-ancestry South African learners. Furthermore, haplotypes of LEP, LEPR and GHRL polymorphisms were associated with varying measurements of weight, BMI and WC. Further studies are required to confirm our results in a larger and homogeneous study population group.

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Genetic variation and decreased risk for obesity in the Atherosclerosis Risk in Communities Study

Abstract: These results suggest that variation within the LEP and MC4R genes is associated with reduced risk for obesity in females.

Cited by 24 publications

References 38 publications

Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins

Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins

Relationship between variants of the leptin gene and obesity and metabolic biomarkers in Brazilian individuals

Association of Cocaine- and Amphetamine-Related Transcript, Leptin and Leptin Receptor Gene Polymorphisms with Anthropometric Obesity Phenotype Indicators in South African Learners

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