Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism/obesity in Pima Indians

Ken Walder, Rod A. Norman, Robert L. Hanson, Patrick Schrauwen, Maria Neverova, Chris P. Jenkinson, Juliet Easlick, Craig H Warden, Claire Pecqueur, Serge Raimbault, Daniel Ricquier, Michael Harper, Kristi Silver, Alan R. Shuldiner, Gemma Solanes, Bradford B. Lowell, Wendy K. Chung, Rudolph L. Leibel, Richard Pratley, Eric Ravussin

Research output: Contribution to journalArticle

262 Citations (Scopus)

Abstract

The UCP2-UCP3 gene cluster maps to chromosome 11q13 in humans, and polymorphisms in these genes may contribute to obesity through effects on energy metabolism. DNA sequencing of UCP2 and UCP3 revealed three polymorphisms informative for association studies: an Ala→Val substitution in exon 4 of UCP2, a 45 bp insertion/deletion in the 3'-untranslated region of exon 8 of UCP2 and a C→T silent polymorphism in exon 3 of UCP3. Initially, 82 young (mean age = 30 ± 7 years), unrelated, full-blooded, non-diabetic Pima Indians were typed for these polymorphisms by direct sequencing. The three sites were in linkage disequilibrium (P < 0.00001). The UCP2 variants were associated with metabolic rate during sleep (exon 4, P = 0.007; exon 8, P = 0.016) and over 24 h (exon 8, P = 0.038). Heterozygotes for UCP2 variants had higher metabolic rates than homozygotes. The UCP3 variant was not significantly associated with metabolic rate or obesity. In a further 790 full-blooded Pima Indians, there was no significant association between the insertion/deletion polymorphism and body mass index (BMI). However, when only individuals > 45 years of age were considered, heterotygotes (subjects with the highest sleeping metabolic rate) had the lowest BMI (P = 0.04). The location of the insertion/deletion polymorphism suggested a role in mRNA stability; however, it appeared to have no effect on skeletal muscle UCP2 mRNA levels in a subset of 23 randomly chosen Pima Indians. In conclusion, these results suggest a contribution from UCP2 (or UCP3) to variation in metabolic rate in young Pima Indians which may contribute to overall body fat content later in life.

Original languageEnglish (US)
Pages (from-to)1431-1435
Number of pages5
JournalHuman Molecular Genetics
Volume7
Issue number9
DOIs
StatePublished - Sep 1998

Fingerprint

Potassium Iodide
Energy Metabolism
Exons
Obesity
Linkage Disequilibrium
RNA Stability
3' Untranslated Regions
Multigene Family
DNA Sequence Analysis
Adipose Tissue
Skeletal Muscle
Chromosomes
Messenger RNA
Genes
Mitochondrial Uncoupling Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Walder, K., Norman, R. A., Hanson, R. L., Schrauwen, P., Neverova, M., Jenkinson, C. P., ... Ravussin, E. (1998). Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism/obesity in Pima Indians. Human Molecular Genetics, 7(9), 1431-1435. https://doi.org/10.1093/hmg/7.9.1431

Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism/obesity in Pima Indians. / Walder, Ken; Norman, Rod A.; Hanson, Robert L.; Schrauwen, Patrick; Neverova, Maria; Jenkinson, Chris P.; Easlick, Juliet; Warden, Craig H; Pecqueur, Claire; Raimbault, Serge; Ricquier, Daniel; Harper, Michael; Silver, Kristi; Shuldiner, Alan R.; Solanes, Gemma; Lowell, Bradford B.; Chung, Wendy K.; Leibel, Rudolph L.; Pratley, Richard; Ravussin, Eric.

In: Human Molecular Genetics, Vol. 7, No. 9, 09.1998, p. 1431-1435.

Research output: Contribution to journalArticle

Walder, K, Norman, RA, Hanson, RL, Schrauwen, P, Neverova, M, Jenkinson, CP, Easlick, J, Warden, CH, Pecqueur, C, Raimbault, S, Ricquier, D, Harper, M, Silver, K, Shuldiner, AR, Solanes, G, Lowell, BB, Chung, WK, Leibel, RL, Pratley, R & Ravussin, E 1998, 'Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism/obesity in Pima Indians', Human Molecular Genetics, vol. 7, no. 9, pp. 1431-1435. https://doi.org/10.1093/hmg/7.9.1431
Walder, Ken ; Norman, Rod A. ; Hanson, Robert L. ; Schrauwen, Patrick ; Neverova, Maria ; Jenkinson, Chris P. ; Easlick, Juliet ; Warden, Craig H ; Pecqueur, Claire ; Raimbault, Serge ; Ricquier, Daniel ; Harper, Michael ; Silver, Kristi ; Shuldiner, Alan R. ; Solanes, Gemma ; Lowell, Bradford B. ; Chung, Wendy K. ; Leibel, Rudolph L. ; Pratley, Richard ; Ravussin, Eric. / Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism/obesity in Pima Indians. In: Human Molecular Genetics. 1998 ; Vol. 7, No. 9. pp. 1431-1435.
@article{4dba3771ffa342138658b9eb9ba82348,
title = "Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism/obesity in Pima Indians",
abstract = "The UCP2-UCP3 gene cluster maps to chromosome 11q13 in humans, and polymorphisms in these genes may contribute to obesity through effects on energy metabolism. DNA sequencing of UCP2 and UCP3 revealed three polymorphisms informative for association studies: an Ala→Val substitution in exon 4 of UCP2, a 45 bp insertion/deletion in the 3'-untranslated region of exon 8 of UCP2 and a C→T silent polymorphism in exon 3 of UCP3. Initially, 82 young (mean age = 30 ± 7 years), unrelated, full-blooded, non-diabetic Pima Indians were typed for these polymorphisms by direct sequencing. The three sites were in linkage disequilibrium (P < 0.00001). The UCP2 variants were associated with metabolic rate during sleep (exon 4, P = 0.007; exon 8, P = 0.016) and over 24 h (exon 8, P = 0.038). Heterozygotes for UCP2 variants had higher metabolic rates than homozygotes. The UCP3 variant was not significantly associated with metabolic rate or obesity. In a further 790 full-blooded Pima Indians, there was no significant association between the insertion/deletion polymorphism and body mass index (BMI). However, when only individuals > 45 years of age were considered, heterotygotes (subjects with the highest sleeping metabolic rate) had the lowest BMI (P = 0.04). The location of the insertion/deletion polymorphism suggested a role in mRNA stability; however, it appeared to have no effect on skeletal muscle UCP2 mRNA levels in a subset of 23 randomly chosen Pima Indians. In conclusion, these results suggest a contribution from UCP2 (or UCP3) to variation in metabolic rate in young Pima Indians which may contribute to overall body fat content later in life.",
author = "Ken Walder and Norman, {Rod A.} and Hanson, {Robert L.} and Patrick Schrauwen and Maria Neverova and Jenkinson, {Chris P.} and Juliet Easlick and Warden, {Craig H} and Claire Pecqueur and Serge Raimbault and Daniel Ricquier and Michael Harper and Kristi Silver and Shuldiner, {Alan R.} and Gemma Solanes and Lowell, {Bradford B.} and Chung, {Wendy K.} and Leibel, {Rudolph L.} and Richard Pratley and Eric Ravussin",
year = "1998",
month = "9",
doi = "10.1093/hmg/7.9.1431",
language = "English (US)",
volume = "7",
pages = "1431--1435",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism/obesity in Pima Indians

AU - Walder, Ken

AU - Norman, Rod A.

AU - Hanson, Robert L.

AU - Schrauwen, Patrick

AU - Neverova, Maria

AU - Jenkinson, Chris P.

AU - Easlick, Juliet

AU - Warden, Craig H

AU - Pecqueur, Claire

AU - Raimbault, Serge

AU - Ricquier, Daniel

AU - Harper, Michael

AU - Silver, Kristi

AU - Shuldiner, Alan R.

AU - Solanes, Gemma

AU - Lowell, Bradford B.

AU - Chung, Wendy K.

AU - Leibel, Rudolph L.

AU - Pratley, Richard

AU - Ravussin, Eric

PY - 1998/9

Y1 - 1998/9

N2 - The UCP2-UCP3 gene cluster maps to chromosome 11q13 in humans, and polymorphisms in these genes may contribute to obesity through effects on energy metabolism. DNA sequencing of UCP2 and UCP3 revealed three polymorphisms informative for association studies: an Ala→Val substitution in exon 4 of UCP2, a 45 bp insertion/deletion in the 3'-untranslated region of exon 8 of UCP2 and a C→T silent polymorphism in exon 3 of UCP3. Initially, 82 young (mean age = 30 ± 7 years), unrelated, full-blooded, non-diabetic Pima Indians were typed for these polymorphisms by direct sequencing. The three sites were in linkage disequilibrium (P < 0.00001). The UCP2 variants were associated with metabolic rate during sleep (exon 4, P = 0.007; exon 8, P = 0.016) and over 24 h (exon 8, P = 0.038). Heterozygotes for UCP2 variants had higher metabolic rates than homozygotes. The UCP3 variant was not significantly associated with metabolic rate or obesity. In a further 790 full-blooded Pima Indians, there was no significant association between the insertion/deletion polymorphism and body mass index (BMI). However, when only individuals > 45 years of age were considered, heterotygotes (subjects with the highest sleeping metabolic rate) had the lowest BMI (P = 0.04). The location of the insertion/deletion polymorphism suggested a role in mRNA stability; however, it appeared to have no effect on skeletal muscle UCP2 mRNA levels in a subset of 23 randomly chosen Pima Indians. In conclusion, these results suggest a contribution from UCP2 (or UCP3) to variation in metabolic rate in young Pima Indians which may contribute to overall body fat content later in life.

AB - The UCP2-UCP3 gene cluster maps to chromosome 11q13 in humans, and polymorphisms in these genes may contribute to obesity through effects on energy metabolism. DNA sequencing of UCP2 and UCP3 revealed three polymorphisms informative for association studies: an Ala→Val substitution in exon 4 of UCP2, a 45 bp insertion/deletion in the 3'-untranslated region of exon 8 of UCP2 and a C→T silent polymorphism in exon 3 of UCP3. Initially, 82 young (mean age = 30 ± 7 years), unrelated, full-blooded, non-diabetic Pima Indians were typed for these polymorphisms by direct sequencing. The three sites were in linkage disequilibrium (P < 0.00001). The UCP2 variants were associated with metabolic rate during sleep (exon 4, P = 0.007; exon 8, P = 0.016) and over 24 h (exon 8, P = 0.038). Heterozygotes for UCP2 variants had higher metabolic rates than homozygotes. The UCP3 variant was not significantly associated with metabolic rate or obesity. In a further 790 full-blooded Pima Indians, there was no significant association between the insertion/deletion polymorphism and body mass index (BMI). However, when only individuals > 45 years of age were considered, heterotygotes (subjects with the highest sleeping metabolic rate) had the lowest BMI (P = 0.04). The location of the insertion/deletion polymorphism suggested a role in mRNA stability; however, it appeared to have no effect on skeletal muscle UCP2 mRNA levels in a subset of 23 randomly chosen Pima Indians. In conclusion, these results suggest a contribution from UCP2 (or UCP3) to variation in metabolic rate in young Pima Indians which may contribute to overall body fat content later in life.

UR - http://www.scopus.com/inward/record.url?scp=7344220905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7344220905&partnerID=8YFLogxK

U2 - 10.1093/hmg/7.9.1431

DO - 10.1093/hmg/7.9.1431

M3 - Article

VL - 7

SP - 1431

EP - 1435

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 9

ER -