GENETIC-MARKERS AT THE LEPTIN (OB) LOCUS ARE NOT SIGNIFICANTLY LINKEDTO HYPERTENSION IN AFRICAN-AMERICANS

Increased body mass index (BMI) has been correlated with increased blo od pressure in human populations. To examine the role of the leptin ge ne (OB) in essential hypertension in African Americans, we performed a ffected sib pair analysis on a set of 103 hypertensive African America n sibships using four highly polymorphic markers at the human leptin l ocus. No evidence of linkage was detected between these markers and th e phenotype of essential hypertension either in these sibships or in a severely obese subset of 46 sibships in which each sibling had a BMI greater than or equal to 85th percentile for the US population. Using BMI rather than hypertension as a quantitative trait, we found signifi cant linkage for the marker D7S504 (P=0.029) but not for the other mar kers. Significance strengthened in the overweight subset of sibships f or this marker (P=0.001), and there was a trend of lower P values for the other three markers. However, multipoint analysis with the use of all four markers simultaneously to estimate linkage between BMI and th e leptin locus did not demonstrate a statistically significant relatio nship. Analysis of the coding region of the leptin gene (exons 2 and 3 ) by single-strand conformational polymorphism revealed a rare Ile-Val polymorphism at amino acid 45 but revealed no other alterations. Thes e results suggest that the OB gene is not a major contributor to the p henotype of essential hypertension in African Americans, although a mi nor contribution to the phenotype of extreme obesity in this group can not be ruled out.