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PMID: 10729112 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

A major susceptibility locus influencing plasma triglyceride concentrations is located on chromosome 15q in Mexican Americans.

American journal of human genetics ·Vol. 66 ·No. 4 ·2000-04-00 ·Pages 1237-45

Duggirala R, Blangero J, Almasy L, Dyer TD, Williams KL, Leach RJ, O'Connell P, Stern MP

Abstract

Although several genetic forms of rare or syndromic hypertriglyceridemia have been reported, little is known about the specific chromosomal regions across the genome harboring susceptibility genes for common forms of hypertriglyceridemia. Therefore, we conducted a genomewide scan for susceptibility genes influencing plasma triglyceride (TG) levels in a Mexican American population. We used both phenotypic and genotypic data from 418 individuals distributed across 27 low-income, extended Mexican American families. For the analyses, TG values were log transformed (ln TG). We used a variance-components technique to conduct multipoint linkage analyses for localizing susceptibility genes that determine variation in TG levels. We used an approximately 10-15-cM map, which was made on the basis of information from 295 microsatellite markers. After accounting for the effects of sex and sex-specific age terms, we found significant evidence for linkage (LOD = 3.88) of ln TG levels to a genetic location between the markers GABRB3 and D15S165 on chromosome 15q. This putative locus explains 39.7+/-7% (P=.000012) of total phenotypic variation in ln TG levels. Suggestive evidence was found for linkage of ln TG levels to two different locations on chromosome 7, which are approximately 85 cM apart from each other. Also, there is some evidence for linkage of high-density lipoprotein cholesterol concentrations to a genetic location near one of the regions on chromosome 7. In conclusion, we found strong evidence for linkage of ln TG levels to a genetic location on chromosome 15q in a Mexican American population, which is prone to disease conditions such as type 2 diabetes and the insulin-resistance syndrome that are associated with hypertriglyceridemia. This putative locus appears to have a major influence on ln TG variation.

MeSH Terms
Adult Cholesterol, HDL/blood Chromosome Mapping Chromosomes, Human, Pair 15/genetics Chromosomes, Human, Pair 7/genetics Coronary Disease/complications,genetics Diabetes Mellitus, Type 2/blood,complications,genetics Female Genetic Predisposition to Disease/genetics Genotype Humans Hypertriglyceridemia/blood,complications,genetics Insulin Resistance/genetics Lod Score Male Mexican Americans/genetics Microsatellite Repeats/genetics Multifactorial Inheritance Phenotype Poverty Receptors, GABA-A/genetics Triglycerides/blood
Chemicals
Cholesterol, HDL Receptors, GABA-A Triglycerides
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Duggirala R
Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. ravi@neel.uthscsa.edu
Blangero J
Almasy L
Dyer T D
Williams K L
Leach R J
O'Connell P
Stern M P
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
Published
2000-04-00
Epub
2000-00-21
Pages
1237-45
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1288191
Subset
IM
Grants
NIDDK NIH HHS · R01 DK53889 · United States
NIDDK NIH HHS · R01 DK47482 · United States
NIDDK NIH HHS · R01 DK047482 · United States
NIGMS NIH HHS · F32 GM018897 · United States
NIDDK NIH HHS · R01 DK42273 · United States
NIMH NIH HHS · R01 MH059490 · United States
NIMH NIH HHS · R37 MH059490 · United States
NIDDK NIH HHS · R01 DK053889 · United States
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