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Genome-Wide Linkage of Plasma Adiponectin Reveals a Major Locus on Chromosome 3q Distinct From the Adiponectin Structural Gene

The IRAS Family Study

¹ Medical Genetics Institute, Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center, Los Angeles, California
² Departments of Pediatrics and Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
³ Division of Clinical Epidemiology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
⁴ Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
⁵ Section of Epidemiology and Community Health, Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado
⁶ Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland
⁷ Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
⁸ Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Address correspondence and reprint requests to Xiuqing Guo, PhD, Medical Genetics Institutes, Cedars-Sinai Medical Center, 8700 Beverly Blvd., 665W, Los Angeles, CA 90048. E-mail: xiuqing.guo{at}cshs.org

Abbreviations: IBD, identity by descent; IRASFS, Insulin Resistance Atherosclerosis Study Family Study; LD, linkage disequilibrium; LOD, logarithm of odds; QTL, quantitative trait locus; SNP, single nucleotide polymorphism; SOLAR, Sequential Oligogenic Analysis Routines; UTR, untranslated region

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.

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