RESUMO
BACKGROUND AND PURPOSE: The aim of this study was to identify quantitative trait loci (QTL) for carotid intima-media thickness (CIMT) a risk factor for stroke and cardiovascular disease. METHODS: Probands were selected from Caribbean Hispanic subjects of the population-based Northern Manhattan Study. CIMT was measured by high-resolution B-mode ultrasound and expressed as the mean (IMTx) and mean of the maximum (IMTm). Variance components methodology was used to detect linkage using SOLAR and calculate locus-specific heritability. Ordered-subset Analysis was done based on history of hypertension and total cholesterol levels. RESULTS: Among 100 Dominican families, 1390 subjects had CIMT measured (848 females; mean age 46.2 years). CIMT had a heritability of 0.65 after adjusting for age, age(2), sex, cigarette pack-years, waist hip ratio, and BMI. Adjusted maximum multipoint LOD scores >2 were found on chromosomes 14q (D14S606) and 7p (D7S817). Linkage to chromosome 14q was significantly increased in a subset of families with the greatest history of hypertension (MLOD=4.12). The QTL on Ch14q accounted for 0.21 of the heritability of IMTm, and on Ch7p 0.27 of the heritability of BIFm. CONCLUSIONS: Several QTLs for CIMT were found on chromosomes 7p and 14q. The QTL on 14q replicates a suggestive linkage peak delimited in the Framingham Heart Study. These QTLs accounted for a substantial amount of trait heritability and warrant further fine mapping.
Assuntos
Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/genética , Ligação Genética/genética , Acidente Vascular Cerebral/genética , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Adulto , Doenças das Artérias Carótidas/etnologia , Mapeamento Cromossômico , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 7/genética , Feminino , Predisposição Genética para Doença/genética , Genótipo , Hispânico ou Latino/etnologia , Hispânico ou Latino/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Locos de Características Quantitativas/genética , Fatores de Risco , Acidente Vascular Cerebral/etnologia , Ultrassonografia , Índias OcidentaisRESUMO
Stroke continues to kill disproportionately more Blacks and Hispanics than Whites in the United States. Racial/ethnic variations in the incidence of stroke and prevalence of stroke risk factors are probably explained by both genetic and environmental influences. Family studies can help identify genetic predisposition to stroke and potential stroke precursors. Few studies have evaluated the heritability of these stroke risk factors among non-White populations, and none have focused on Caribbean Hispanic populations. The aim of the Northern Manhattan Family Study (NOMAFS) is to investigate the gene-environment interaction of stroke risk factors among Caribbean Hispanics. The unique recruitment and methodologic approaches used in this study are relevant to the design and conduct of genetic aggregation studies to investigate complex genetic disorders in non-White populations. The aim of this paper is to describe the NOMAFS and report enrollment and characteristics of the participants. The NOMAFS will provide a data resource for the exploration of the genetic determinants of highly heritable stroke precursor phenotypes that are less complex than the stroke phenotype. Understanding the gene environment interaction is the critical next step toward the development of new and unique approaches to disease prevention and interventions.