Association of genetic variation within UBL5 with phenotypes of metabolic syndrome

Kiymet Bozaoglu, Joanne E. Curran, Kate S. Elliott, Ken R. Walder, Thomas D. Dyer, David L. Rainwater, John L. Vandeberg, Anthony G. Comuzzie, Greg R. Collier, Paul Zimmet, Jean W. MacCluer, Jeremy B. Jowett, John Blangero

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The BEACON gene was initially identified using the differential display polymerase chain reaction on hypothalamic mRNA samples collected from lean and obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON gene expression was positively correlated with percentage of body fat. and intracerebroventricular infusion of the Beacon protein resulted in a dose-dependent increase in food intake and body weight. The human homolog of BEACON. UBL5, is located on chromosome 19p in a region previously linked to quantitative traits related to obesity. Our previous studies showed a statistically significant association between UBL5 sequence variation and several obesity- and diabetes-related quantitative physiological measures in Asian Indian and Micronesian cohorts. Here we undertake a replication study in a Mexican American cohort where the original linkage signal was first detected. We exhaustively resequenced the complete gene plus the putative promoter region for genetic variation in 55 individuals and identified five single nucleotide polymorphisms (SNPs). one of which was novel. These SNPs were genotyped in a Mexican American cohort of 900 individuals from 40 families. Using a quantitative trait linkage disequilibrium test, we found significant associations between UBL5 genetic variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals. These data are consistent with our earlier published studies and further support a functional role for the UBL5 gene in influencing physiological traits that underpin the development of metabolic syndrome.

LanguageEnglish
Pages147-159
Number of pages13
JournalHuman Biology
Volume78
Issue number2
Publication statusPublished - Apr 2006

Keywords

  • BEACON gene
  • Diabetes
  • Dyslipidemia
  • Mauritians
  • Metabolic syndrome
  • Mexican Americans
  • Nauruans
  • San Antonio Family Heart Study
  • UBL5

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Genetics(clinical)

Cite this

Bozaoglu, K., Curran, J. E., Elliott, K. S., Walder, K. R., Dyer, T. D., Rainwater, D. L., ... Blangero, J. (2006). Association of genetic variation within UBL5 with phenotypes of metabolic syndrome. Human Biology, 78(2), 147-159.
Bozaoglu, Kiymet ; Curran, Joanne E. ; Elliott, Kate S. ; Walder, Ken R. ; Dyer, Thomas D. ; Rainwater, David L. ; Vandeberg, John L. ; Comuzzie, Anthony G. ; Collier, Greg R. ; Zimmet, Paul ; MacCluer, Jean W. ; Jowett, Jeremy B. ; Blangero, John. / Association of genetic variation within UBL5 with phenotypes of metabolic syndrome. In: Human Biology. 2006 ; Vol. 78, No. 2. pp. 147-159.
@article{f099aa427fa140c6b9585d99666ec3a5,
title = "Association of genetic variation within UBL5 with phenotypes of metabolic syndrome",
abstract = "The BEACON gene was initially identified using the differential display polymerase chain reaction on hypothalamic mRNA samples collected from lean and obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON gene expression was positively correlated with percentage of body fat. and intracerebroventricular infusion of the Beacon protein resulted in a dose-dependent increase in food intake and body weight. The human homolog of BEACON. UBL5, is located on chromosome 19p in a region previously linked to quantitative traits related to obesity. Our previous studies showed a statistically significant association between UBL5 sequence variation and several obesity- and diabetes-related quantitative physiological measures in Asian Indian and Micronesian cohorts. Here we undertake a replication study in a Mexican American cohort where the original linkage signal was first detected. We exhaustively resequenced the complete gene plus the putative promoter region for genetic variation in 55 individuals and identified five single nucleotide polymorphisms (SNPs). one of which was novel. These SNPs were genotyped in a Mexican American cohort of 900 individuals from 40 families. Using a quantitative trait linkage disequilibrium test, we found significant associations between UBL5 genetic variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals. These data are consistent with our earlier published studies and further support a functional role for the UBL5 gene in influencing physiological traits that underpin the development of metabolic syndrome.",
keywords = "BEACON gene, Diabetes, Dyslipidemia, Mauritians, Metabolic syndrome, Mexican Americans, Nauruans, San Antonio Family Heart Study, UBL5",
author = "Kiymet Bozaoglu and Curran, {Joanne E.} and Elliott, {Kate S.} and Walder, {Ken R.} and Dyer, {Thomas D.} and Rainwater, {David L.} and Vandeberg, {John L.} and Comuzzie, {Anthony G.} and Collier, {Greg R.} and Paul Zimmet and MacCluer, {Jean W.} and Jowett, {Jeremy B.} and John Blangero",
year = "2006",
month = "4",
language = "English",
volume = "78",
pages = "147--159",
journal = "Human Biology",
issn = "0018-7143",
publisher = "Wayne State University Press",
number = "2",

}

Bozaoglu, K, Curran, JE, Elliott, KS, Walder, KR, Dyer, TD, Rainwater, DL, Vandeberg, JL, Comuzzie, AG, Collier, GR, Zimmet, P, MacCluer, JW, Jowett, JB & Blangero, J 2006, 'Association of genetic variation within UBL5 with phenotypes of metabolic syndrome', Human Biology, vol. 78, no. 2, pp. 147-159.

Association of genetic variation within UBL5 with phenotypes of metabolic syndrome. / Bozaoglu, Kiymet; Curran, Joanne E.; Elliott, Kate S.; Walder, Ken R.; Dyer, Thomas D.; Rainwater, David L.; Vandeberg, John L.; Comuzzie, Anthony G.; Collier, Greg R.; Zimmet, Paul; MacCluer, Jean W.; Jowett, Jeremy B.; Blangero, John.

In: Human Biology, Vol. 78, No. 2, 04.2006, p. 147-159.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of genetic variation within UBL5 with phenotypes of metabolic syndrome

AU - Bozaoglu, Kiymet

AU - Curran, Joanne E.

AU - Elliott, Kate S.

AU - Walder, Ken R.

AU - Dyer, Thomas D.

AU - Rainwater, David L.

AU - Vandeberg, John L.

AU - Comuzzie, Anthony G.

AU - Collier, Greg R.

AU - Zimmet, Paul

AU - MacCluer, Jean W.

AU - Jowett, Jeremy B.

AU - Blangero, John

PY - 2006/4

Y1 - 2006/4

N2 - The BEACON gene was initially identified using the differential display polymerase chain reaction on hypothalamic mRNA samples collected from lean and obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON gene expression was positively correlated with percentage of body fat. and intracerebroventricular infusion of the Beacon protein resulted in a dose-dependent increase in food intake and body weight. The human homolog of BEACON. UBL5, is located on chromosome 19p in a region previously linked to quantitative traits related to obesity. Our previous studies showed a statistically significant association between UBL5 sequence variation and several obesity- and diabetes-related quantitative physiological measures in Asian Indian and Micronesian cohorts. Here we undertake a replication study in a Mexican American cohort where the original linkage signal was first detected. We exhaustively resequenced the complete gene plus the putative promoter region for genetic variation in 55 individuals and identified five single nucleotide polymorphisms (SNPs). one of which was novel. These SNPs were genotyped in a Mexican American cohort of 900 individuals from 40 families. Using a quantitative trait linkage disequilibrium test, we found significant associations between UBL5 genetic variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals. These data are consistent with our earlier published studies and further support a functional role for the UBL5 gene in influencing physiological traits that underpin the development of metabolic syndrome.

AB - The BEACON gene was initially identified using the differential display polymerase chain reaction on hypothalamic mRNA samples collected from lean and obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON gene expression was positively correlated with percentage of body fat. and intracerebroventricular infusion of the Beacon protein resulted in a dose-dependent increase in food intake and body weight. The human homolog of BEACON. UBL5, is located on chromosome 19p in a region previously linked to quantitative traits related to obesity. Our previous studies showed a statistically significant association between UBL5 sequence variation and several obesity- and diabetes-related quantitative physiological measures in Asian Indian and Micronesian cohorts. Here we undertake a replication study in a Mexican American cohort where the original linkage signal was first detected. We exhaustively resequenced the complete gene plus the putative promoter region for genetic variation in 55 individuals and identified five single nucleotide polymorphisms (SNPs). one of which was novel. These SNPs were genotyped in a Mexican American cohort of 900 individuals from 40 families. Using a quantitative trait linkage disequilibrium test, we found significant associations between UBL5 genetic variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals. These data are consistent with our earlier published studies and further support a functional role for the UBL5 gene in influencing physiological traits that underpin the development of metabolic syndrome.

KW - BEACON gene

KW - Diabetes

KW - Dyslipidemia

KW - Mauritians

KW - Metabolic syndrome

KW - Mexican Americans

KW - Nauruans

KW - San Antonio Family Heart Study

KW - UBL5

UR - http://www.scopus.com/inward/record.url?scp=33749549273&partnerID=8YFLogxK

M3 - Article

VL - 78

SP - 147

EP - 159

JO - Human Biology

T2 - Human Biology

JF - Human Biology

SN - 0018-7143

IS - 2

ER -

Bozaoglu K, Curran JE, Elliott KS, Walder KR, Dyer TD, Rainwater DL et al. Association of genetic variation within UBL5 with phenotypes of metabolic syndrome. Human Biology. 2006 Apr;78(2):147-159.