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PMID: 8751871 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7.

American journal of human genetics ·Vol. 59 ·No. 3 ·1996-09-00 ·Pages 694-703

Duggirala R, Stern MP, Mitchell BD, Reinhart LJ, Shipman PA, Uresandi OC, Chung WK, Leibel RL, Hales CN, O'Connell P, Blangero J

Abstract

Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and approximately 73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is approximately 15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans.

MeSH Terms
Adult Blood Glucose/metabolism Carboxypeptidases/genetics Carboxypeptidases A Chromosomes, Human, Pair 7/genetics Diabetes Mellitus, Type 2/genetics Female Genetic Linkage Genetic Variation/genetics Humans Insulin/blood Leptin Male Mexican Americans/genetics Microsatellite Repeats Middle Aged Multivariate Analysis Obesity/blood,genetics Proinsulin/blood Proteins/genetics Skinfold Thickness
Chemicals
Blood Glucose Insulin Leptin Proteins Proinsulin Carboxypeptidases Carboxypeptidases A
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Duggirala R
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7873, USA. ravi@gauss.uthscsa.edu
Stern M P
Mitchell B D
Reinhart L J
Shipman P A
Uresandi O C
Chung W K
Leibel R L
Hales C N
O'Connell P
Blangero J
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
Email
ravi@gauss.uthscsa.edu
Published
1996-09-00
Pages
694-703
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1914918
Subset
IM
Grants
NIDDK NIH HHS · P30 DK026687 · United States
NIDDK NIH HHS · DK42273 · United States
NIDDK NIH HHS · DK44297 · United States
NIDDK NIH HHS · DK47482 · United States
External Links
PubMed source PMC Full Text View journal details
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