Coincident Linkage of Fasting Plasma Insulin and Blood Pressure to Chromosome 7q in Hypertensive Hispanic Families

Li, Cheng; Davis, Richard C.; Raffel, Leslie J.; Xiang, Anny H.; Wang, N.; Quiñones, Manuel J.; Wen, Ping; Toscano, Edgar; Díaz, José A.; Pressman, Sarah D.; Henderson, Paula; Azen, Stanley P.; Hsueh, Wen‐Chi; Buchanan, Thomas A.; Rotter, Jerome I.

doi:10.1161/hc3601.096729

Cited by 83 publications

(70 citation statements)

References 33 publications

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“…These "surrogate" measures of physiological processes appear to have different genetic architecture from these directly measured parameters (8). Three studies with the preferred direct measurements of glucose homeostasis are the FUSION (Finland-U.S. Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics) study (31), the study of hypertension and insulin resistance in Hispanics (13,32), and the HERITAGE Family Study (33). FUSION investigators conducted a genome scan for type 2 diabetes-associated quantitative traits in 580 Finnish families.…”

Section: Discussionmentioning

confidence: 99%

Identification of Quantitative Trait Loci for Glucose Homeostasis

et al. 2004

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Genetic and environmental determinants play critical roles in insulin resistance and ␤-cell function. A model of the complex feedback system for maintenance of glucose tolerance has been developed that reflects the constraint of glycemia within narrow physiologic limits. The "glucose homeostasis" model is described by insulin sensitivity (S I ), glucose disposition (S G ), acute insulin response to glucose (AIR G ), and disposition index (DI). Relatively little is known about the genetic basis of glucose homeostasis phenotypes or their relationship to risk of diabetes and atherosclerotic cardiovascular disease. A genome scan for glucose homeostasis phenotypes in nondiabetic subjects has been carried out in African-American (n ‫؍‬ 21) and Hispanic (n ‫؍‬ 45) extended families as part of the IRAS Family Study. In African-American families, there was significant evidence for linkage of DI between D11S2371 and D11S2002 (logarithm of odds [LOD] ‫؍‬ 3.21) at 81 cM, and in the combined sample of African-American and Hispanic families, there was evidence at GATA117D01 (140 cM) on chromosome 11 (LOD ‫؍‬ 2.21). Evidence of linkage was also observed for S I in Hispanic (LOD ‫؍‬ 2.28, between D15S822 and GTTTT001) and AIR G in African-American families (LOD ‫؍‬ 2.73, between D4S1625 and D4S1629; and LOD ‫؍‬ 2.56 at PAH (phenylalanine hydroxylase) on chromosome 12). These results provide impetus for future positional cloning of quantitative trait loci (QTLs). Identifying genes in these regions should provide insight into the nature of the metabolic syndrome and diabetes, and facilitate the development of more effective therapies for prevention and treatment of diabetes and other diseases associated with disordered glucose metabolism.

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Section: Discussionmentioning

confidence: 99%

Identification of Quantitative Trait Loci for Glucose Homeostasis

et al. 2004

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“…For example, insulin sensitivity or insulin resistance is often estimated using fasting glucose, fasting insulin, or calculations based on these measurements, which are convenient to obtain in population samples and have been successfully used to reveal novel hypertension loci. 106 However, even these simple measurements are less reliable than the direct quantification of insulin sensitivity, using physiological studies such as the frequently sampled intravenous glucose tolerance test or the euglycemic clamp. 107 This suggests that the precision of the physiological study is of key importance when measuring the phenotype.…”

Section: Genetic Markers: Approaches To Defining Cardiovascular Diseamentioning

confidence: 99%

Genetic Markers

et al. 2004

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“…12 This cosegregation was further confirmed in our genome scan linkage analysis, wherein we identified several regions of coincident linkage of insulin sensitivity and BP. 13 For example, fasting insulin, SBP, and mean arterial blood pressure were all mapped to the same region on chromosome 7 (112 to 128 cM). Considered together, these findings provide strong support for the concept that IR is an intermediate and genetically regulated phenotype for HTN.…”

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Hypertension Genes Are Genetic Markers for Insulin Sensitivity and Resistance

et al. 2005

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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 (nϭ656) 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 (nϭ449). AGT M235T and NOS3 A(Ϫ922)G and E298D polymorphisms were significantly associated with insulin sensitivity (Pϭ0.018, 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 (Pϭ0.015 and 0.028). (HTN) is not benign; it is strongly associated with the development of atherosclerosis and left ventricular hypertrophy resulting in congestive heart failure, stroke, and age-related macular degeneration. 1-2 The risk of complications increases with increasing blood pressure (BP), particularly systolic blood pressure (SBP). 3,4 High BP is also a major antecedent for renal failure and, after diabetes, is the second most common cause of chronic renal failure in the adult population. 1,5 Insulin resistance (IR) is a potentially important intermediate phenotype for HTN in certain populations, particularly in Mexican Americans (MAs). Cross-sectional studies have revealed correlations between IR and BP in this and other ethnic groups. 6 -8 Hyperinsulinemia preceded and predicted the development of HTN in an 8-year prospective study of MAs in San Antonio, Texas 6 and has exhibited major gene effects in at least 3 ethnic groups. 9 -11 By path analysis, we have shown that BP and IR cosegregate and have a significant genetic component independent of any relationship to body mass index (BMI). 12 This cosegregation was further confirmed in our genome scan linkage analysis, wherein we identified several regions of coincident linkage of insulin sensitivity and BP. 13 For example, fasting insulin, SBP, and mean arterial blood pressure were all mapped to the same region on chromosome 7 (112 to 128 cM). Considered together, these findings provide strong support for the concept that IR is an intermediate and genetically regulated phenotype for HTN.Although the aforementioned data may suggest that IR is a proximate cause of HTN, an alternative possibility is that both are pleiotropic manifestations of the same underlying susceptibility. In support of this latter hypothesis has been the observation that several large scale clinical trials of pharmacological agents whose targets are t...

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Coincident Linkage of Fasting Plasma Insulin and Blood Pressure to Chromosome 7q in Hypertensive Hispanic Families

Cited by 83 publications

References 33 publications

Identification of Quantitative Trait Loci for Glucose Homeostasis

Identification of Quantitative Trait Loci for Glucose Homeostasis

Genetic Markers

Hypertension Genes Are Genetic Markers for Insulin Sensitivity and Resistance

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