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Adiponectin (APM1) is an adipocyte-derived peptide that contributes to glucose, lipid, and energy homeostasis. We assessed the genetic basis of plasma adiponectin in Hispanic-American and African-American families enrolled through the Insulin Resistance Atherosclerosis Study Family Study. A 10-cM genome scan was performed in two batches: an original set (set 1) consisting of 66 families (45 Hispanic American and 21 African American) and a replication set (set 2) consisting of 66 families (45 Hispanic American and 21 African American). Adiponectin levels were measured by radioimmunoassay in 1,727 individuals from 131 of 132 families. Linkage analysis was carried out in Hispanic Americans and African Americans separately in set 1, set 2, and the pooled set (set 1 plus set 2), with and without diabetic subjects. A major gene was mapped to 3q27 with a logarithm of odds (LOD) score of 8.21 in the Hispanic-American sample. Ninety-six unrelated individuals were screened for polymorphisms in the APM1 gene, and 18 single nucleotide polyporphisms (SNPs) were genotyped in the Hispanic-American sample. Plasma adiponectin level was modestly associated with two SNPs and their accompaning haplotypes. Incorporating each or both SNPs in the linkage analysis, however, did not significantly reduce the LOD score. Therefore, a quantitative trait locus at 3q27, likely distinct from the APM1 gene, contributes to the variation of plasma adiponectin levels in the Hispanic-American population., Plasma adiponectin is an adipocytokine produced by fat cells; its concentration was found to be negatively correlated with BMI, insulin resistance, hyperinsulinemia, plasma triglyceride concentration, and fasting and postprandial plasma [...]

Glucose homeostasis, a defining characteristic of physiological glucose metabolism, is the result of complex feedback relationships with both genetic and environmental determinants that influence insulin sensitivity and β-cell function. Relatively [...]

The metabolic syndrome is characterized by central obesity, dyslipidemia, elevated blood pressure, and hyperglycemia. The Insulin Resistance Atherosclerosis Study (IRAS) Family Study recruited extended pedigrees of Hispanic descent from San Antonio, TX (SA) and San Luis Valley, CO (SLV). Thirty-five of these pedigrees (27 SA and 8 SLV) had at least 2 individuals with metabolic syndrome (216 affected individuals and 563 affected relative pairs). The prevalence of metabolic syndrome and component criteria in subjects from these pedigrees were 35% metabolic syndrome, 43% increased waist circumference, 31% hypertriglyceridemia, 69% low HDL cholesterol, 31% increased blood pressure, and 25% either increased fasting glucose or presence of diabetes. Nonparametric linkage analysis provided evidence for linkage of metabolic syndrome to 1q23-q31 (D1S518; logarithm of odds [LOD] 1.6) with significant site heterogeneity (SA LOD 2.6 and SLV LOD 0.0), and removing all individuals with diabetes reduced, but did not eliminate, the evidence for linkage to this region (LOD 1.2). This heterogeneity may partially be explained by phenotypic differences. Members in the SA pedigrees were older, had greater central obesity, had higher prevalence of the metabolic syndrome, and were from a more urban environment than members of the SLV pedigrees. These results contribute to the growing evidence that chromosome 1q harbors at least one locus related to the metabolic precursors of diabetes., The metabolic syndrome is a clinical entity consisting of central obesity, dyslipidemia, elevated blood pressure, and hyperglycemia, and its presence is associated with an increased risk for type 2 diabetes [...]

African Americans are at increased risk of type 2 diabetes and many diabetes complications. We have carried out a genome-wide scan for African American type 2 diabetes using 638 affected sibling pairs (ASPs) from 247 families ascertained through impaired renal function to identify type 2 diabetes loci in this high-risk population. Of the 638 ASPs, 210 were concordant for diabetes with impaired renal function. A total of 390 markers, at an average spacing of 9 cM, were genotyped by the Center for Inherited Disease Research (CIDR) as part of the International Type 2 Diabetes Linkage Analysis Consortium. Nonparametric linkage (NPL) analyses conducted using the exponential model implemented in Genehunter Plus provided suggestive evidence for linkage at 6q24-q27 (163.5 cM, logarithm of odds [LOD] 2.26). Multilocus NPL regression analysis identified the 6q locus (D6S1035, LOD 2.67) and two additional regions: 7p (LOD 1.06) and 18q (LOD 0.87) as important in this model. NPL regression-based interaction analyses and ordered subset analyses (OSAs) supported the presence of a locus at chromosome 7p (29-34 cM) in the pedigrees with the earliest mean age of diagnosis of type 2 diabetes (P = 0.009 for interaction, ΔP = 0.0034 for OSA) and lower mean BMI (P = 0.009 for interaction, ΔP = 0.070 for OSA). These results provide evidence that genes predisposing African-American individuals to type 2 diabetes are located in the 6q and 7p regions of the genome. Diabetes 53:830-837, 2004, An African-American individual is twice as likely to develop type 2 diabetes as a Caucasian American peer (1,2), and it is estimated that 2.8 million African Americans (13% of this [...]