Details

Autor(en) / Beteiligte

• POLLIN, Toni I
• TANNER, Keith
• O'CONNELL, Jeffrey R
• OTT, Sandra H
• DAMCOTT, Coleen M
• SHULDINER, Alan R
• MCLENITHAN, John C
• MITCHELL, Braxton D

Titel

Linkage of Plasma Adiponectin Levels to 3q27 Explained by Association With Variation in the APM1 Gene

Ist Teil von

• Diabetes (New York, N.Y.), 2005-01, Vol.54 (1), p.268-274

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2005

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Linkage of Plasma Adiponectin Levels to 3q27 Explained by Association With Variation in the APM1 Gene Toni I. Pollin 1 , Keith Tanner 1 , Jeffrey R. O’Connell 1 , Sandra H. Ott 1 , Coleen M. Damcott 1 , Alan R. Shuldiner 1 2 , John C. McLenithan 1 and Braxton D. Mitchell 1 1 University of Maryland School of Medicine, Baltimore, Maryland 2 Baltimore Veterans Affairs Medical Center, Geriatric Research, Education and Clinical Center, Baltimore, Maryland Address correspondence and reprint requests to Toni I. Pollin, PhD, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, 660 W. Redwood St., Rm. 478, Baltimore, MD 21201 E-mail: tpollin{at}medicine.umaryland.edu Abstract We performed a genome-wide linkage scan of plasma adiponectin levels in 569 nondiabetic participants in the Amish Family Diabetes Study. The highest logarithm of odds (LOD) score (2.13; P = 0.0009) occurred on chromosome 3q27 between markers D3S1602 and D3S1580, which flank APM1/ACDC , the adiponectin gene. The APM1 +2019 A/− insertion/deletion polymorphism in the 3′ untranslated region (single nucleotide polymorphism [SNP] +2019; deletion allele frequency 0.30 in Amish) showed strong association with adiponectin levels in a dosage-dependent manner in a direction consistent with that reported in previous studies, with deletion heterozygosity increasing adiponectin levels by 1.3 ± 0.5 μg/ml and deletion homozygosity increasing levels by 3.0 ± 0.8 μg/ml ( P < 0.0001). Two other SNPs, rs2241766 and rs1501299, showed moderate association. In a subset of 523 subjects genotyped for both SNP +2019 and rs2241766, including the APM1 SNP +2019 genotype as a covariate reduced the linkage signal at 3q27 by 1.26 LOD units (from 2.22 to 0.96) and including both SNPs reduced the signal by 1.51 LOD units (to 0.71). These findings, combined with a two-point LOD score of 2.35 for SNP +2019, provide evidence that variation in APM1 is responsible for linkage of adiponectin levels to 3q27 in the Old Order Amish. AFDS, Amish Family Diabetes Study LD, linkage disequilibrium QTL, quantitative trait locus SNP, single nucleotide polymorphism SOLAR, Sequential Oligogenic Linkage Analysis Routines UTR, untranslated region Footnotes Accepted September 15, 2004. Received July 1, 2004. DIABETES