Novel variants in the putative peroxisome proliferator-activated receptor {gamma} promoter and relationships with obesity in men

TY - JOUR

T1 - Novel variants in the putative peroxisome proliferator-activated receptor {gamma} promoter and relationships with obesity in men

AU - Larsen, Thomas M

AU - Larsen, Lesli H

AU - Torekov, Signe K

AU - Ek, Jakob

AU - Black, Eva

AU - Toubro, Søren

AU - Astrup, Arne

AU - Sørensen, Thorkild I A

AU - Hansen, Torben

AU - Pedersen, Oluf

PY - 2005

Y1 - 2005

N2 - Yet unidentified variants within the peroxisome proliferator-activated receptor gamma (PPARgamma) 2 promoter may explain the inconsistent reports on associations between variants in the coding region and obesity or diabetes. Thus, we examined the putative PPARgamma2 promoter (-3371 to +43 bp) for variants in 83 subjects with obesity or type 2 diabetes. We identified eight variants, seven of which were novel, including -792A>G, -816C>T, -882T>C, -1505G>A, -1881C>T, -1884T>A, -2604T>C, and -2953A>G. The variants -816C>T, -1505G>A, -1881C>T, and -2604T>C were in total linkage disequilibrium, and there was a high degree of linkage disequilibrium between several of the novel variants and Pro12Ala. The novel variants were, together with Pro12Ala and 1431C>T, examined for relationships with obesity among 234 men with early-onset obesity with a BMI at age approximately 20 years of 33.2+/-2.5 kg/m2 and 323 nonobese men with a BMI of 21.7+/-2.5 kg/m2, who were also reexamined after approximately 29 years. The prevalence of the identified variants was not significantly different between the two groups, and the variants did not affect changes in BMI over time. In conclusion, the identified novel variants in the PPARgamma2 promoter region do not explain the reported discrepancies in the association of previously identified variants with obesity and type 2 diabetes.

AB - Yet unidentified variants within the peroxisome proliferator-activated receptor gamma (PPARgamma) 2 promoter may explain the inconsistent reports on associations between variants in the coding region and obesity or diabetes. Thus, we examined the putative PPARgamma2 promoter (-3371 to +43 bp) for variants in 83 subjects with obesity or type 2 diabetes. We identified eight variants, seven of which were novel, including -792A>G, -816C>T, -882T>C, -1505G>A, -1881C>T, -1884T>A, -2604T>C, and -2953A>G. The variants -816C>T, -1505G>A, -1881C>T, and -2604T>C were in total linkage disequilibrium, and there was a high degree of linkage disequilibrium between several of the novel variants and Pro12Ala. The novel variants were, together with Pro12Ala and 1431C>T, examined for relationships with obesity among 234 men with early-onset obesity with a BMI at age approximately 20 years of 33.2+/-2.5 kg/m2 and 323 nonobese men with a BMI of 21.7+/-2.5 kg/m2, who were also reexamined after approximately 29 years. The prevalence of the identified variants was not significantly different between the two groups, and the variants did not affect changes in BMI over time. In conclusion, the identified novel variants in the PPARgamma2 promoter region do not explain the reported discrepancies in the association of previously identified variants with obesity and type 2 diabetes.

KW - Body Mass Index

KW - Chromosome Mapping

KW - Cohort Studies

KW - DNA

KW - Diabetes Mellitus, Type 2

KW - Follow-Up Studies

KW - Genetic Variation

KW - Genotype

KW - Humans

KW - Linkage Disequilibrium

KW - Male

KW - Middle Aged

KW - Obesity

KW - PPAR gamma

KW - Promoter Regions, Genetic

KW - Sequence Analysis, DNA

KW - Statistics, Nonparametric

U2 - 10.1038/oby.2005.110

DO - 10.1038/oby.2005.110

M3 - Journal article

C2 - 15976135

SN - 1071-7323

VL - 13

SP - 953

EP - 958

JO - Obesity Research

JF - Obesity Research

IS - 6

ER -