title: Hypertension genes are genetic markers for insulin sensitivity and resistance.
abstract: Insulin resistance is a determinant of blood pressure variation and risk factor for hypertension. Because insulin resistance and blood pressure cosegregate in Mexican American families, we thus investigated the association between variations in 9 previously reported hypertension genes (ACE, AGT, AGTRI, ADDI, NPPA, ADDRB2, SCNN1A, GNB3, and NOS3) and insulin resistance. Families were ascertained via a coronary artery disease proband in the Mexican American Coronary Artery Disease Project. Individuals from 100 Mexican American families (n=656) were genotyped for 14 polymorphisms in the 9 genes and all adult offspring and offspring spouses were phenotyped for insulin sensitivity by hyperinsulinemic euglycemic clamp (n=449). AGT M235T and NOS3 A(-922)G and E298D polymorphisms were significantly associated with insulin sensitivity (P=0.018, 0.036, 0.039) but were not significant after adjusting for body mass index. ADD1 G460W was associated with insulin sensitivity only after adjusting for body mass index. The NPPA T2238C and SCNN1A A663T were associated with decreased fasting insulin levels after adjusting for body mass index (P=0.015 and 0.028). In conclusion, AGT, NOS3, NPPA, ADRB2, ADD1, and SCNN1A may well be genetic markers for insulin resistance, and adiposity was a potential modifier for only some gene/trait combinations. Our data support the hypothesis that genes in the blood pressure pathway may play a role in insulin resistance in Mexican Americans.
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, Calif 90048, USA. Xiuqing.Guo@cshs.org
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.forename: Suzanne
authors.initials: S
authors.lastname: Cheng
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Jinrui
authors.initials: J
authors.lastname: Cui
authors.forename: Randall
authors.initials: R
authors.lastname: Hughes
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Quiñones
authors.forename: Isabel
authors.initials: I
authors.lastname: Bulnes-Enriquez
authors.forename: Roxana
authors.initials: R
authors.lastname: De la Rosa
authors.forename: George
authors.initials: G
authors.lastname: Aurea
authors.forename: Huiying
authors.initials: H
authors.lastname: Yang
authors.forename: Willa
authors.initials: W
authors.lastname: Hsueh
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
mesh_terms: D000328:Adult; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers; D007328:Insulin