Background: Insulin resistance (IR) and hyperinsulinemia are phenotypically associated with hypertension. We have previously provided evidence that blood pressure (BP) and IR cosegregate in Hispanic families, suggesting that this association has a genetic component. In the present study, we provide further support for the hypothesis of a genetic basis for the BP-IR relationship from a genetic linkage study.
Methods and results: A 10-cM genome scan was conducted in 390 Hispanic family members of 77 hypertensive probands. Detailed measurements of BP, glucose, insulin levels, and insulin sensitivity (euglycemic clamp) were performed in adult offspring of probands. Multipoint variance component linkage analysis was used. A region on chromosome 7q seemed to influence both IR and BP. The greatest evidence for linkage was found for fasting insulin (lod score=3.36 at 128 cM), followed by systolic BP (lod score=2.06 at 120 cM). Fine mapping with greater marker density in this region increased the maximum lod score for fasting insulin to 3.94 at 125 cM (P=0.00002); lod score for systolic BP was 2.51 at 112 cM. Coincident mapping at this locus also included insulin sensitivity measured by the homeostasis assessment model (HOMA) and serum leptin concentrations. Insulin sensitivity by euglycemic clamp did not map to the same locus.
Conclusions: Our results demonstrate that a major gene determining fasting insulin is located on chromosome 7q. Linkage of BP, HOMA, and leptin levels to the same region suggests this locus may broadly influence traits associated with IR and supports a genetic basis for phenotypic associations in IR syndrome.