Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Medical Genetics
Published in: BMC Medical Genetics 1/2009

Open Access 01-12-2009 | Research article

Suggestion for linkage of chromosome 1p35.2 and 3q28 to plasma adiponectin concentrations in the GOLDN Study

Authors: Laura J Rasmussen-Torvik, James S Pankow, James M Peacock, Ingrid B Borecki, James E Hixson, Michael Y Tsai, Edmond K Kabagambe, Donna K Arnett

Published in: BMC Medical Genetics | Issue 1/2009

Login to get access

Abstract

Background

Adiponectin is inversely associated with obesity, insulin resistance, and atherosclerosis, but little is known about the genetic pathways that regulate the plasma level of this protein. To find novel genes that influence circulating levels of adiponectin, a genome-wide linkage scan was performed on plasma adiponectin concentrations before and after 3 weeks of treatment with fenofibrate (160 mg daily) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. We studied Caucasian individuals (n = 1121) from 190 families in Utah and Minnesota. Of these, 859 individuals from 175 families had both baseline and post-fenofibrate treatment measurements for adiponectin. Plasma adiponectin concentrations were measured with an ELISA assay. All participants were typed for microsatellite markers included in the Marshfield Mammalian Genotyping Service marker set 12, which includes 407 markers spaced at approximately 10 cM regions across the genome. Variance components analysis was used to estimate heritability and to perform genome-wide scans. Adiponectin was adjusted for age, sex, and field center. Additional models also included BMI adjustment.

Results

Baseline and post-fenofibrate adiponectin measurements were highly correlated (r = 0.95). Suggestive (LOD > 2) peaks were found on chromosomes 1p35.2 and 3q28 (near the location of the adiponectin gene).

Conclusion

Two candidate genes, IL22RA1 and IL28RA, lie under the chromosome 1 peak; further analyses are needed to identify the specific genetic variants in this region that influence circulating adiponectin concentrations.
Appendix
Available only for authorised users
Literature
1.
Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, et al: The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001, 7 (8): 941-946. 10.1038/90984.CrossRefPubMed
2.
Lihn AS, Bruun JM, He G, Pedersen SB, Jensen PF, Richelsen B: Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese subjects. Mol Cell Endocrinol. 2004, 219 (1–2): 9-15. 10.1016/j.mce.2004.03.002.CrossRefPubMed
3.
Park KG, Park KS, Kim MJ, Kim HS, Suh YS, Ahn JD, Park KK, Chang YC, Lee IK: Relationship between serum adiponectin and leptin concentrations and body fat distribution. Diabetes Res Clin Pract. 2004, 63 (2): 135-142. 10.1016/j.diabres.2003.09.010.CrossRefPubMed
4.
Shand BI, Scott RS, Elder PA, George PM: Plasma adiponectin in overweight, nondiabetic individuals with or without insulin resistance. Diabetes Obes Metab. 2003, 5 (5): 349-353. 10.1046/j.1463-1326.2003.00279.x.CrossRefPubMed
5.
Tschritter O, Fritsche A, Thamer C, Haap M, Shirkavand F, Rahe S, Staiger H, Maerker E, Haring H, Stumvoll M: Plasma adiponectin concentrations predict insulin sensitivity of both glucose and lipid metabolism. Diabetes. 2003, 52 (2): 239-243. 10.2337/diabetes.52.2.239.CrossRefPubMed
6.
Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA: Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001, 86 (5): 1930-1935. 10.1210/jc.86.5.1930.CrossRefPubMed
7.
Matsuda M, Shimomura I, Sata M, Arita Y, Nishida M, Maeda N, Kumada M, Okamoto Y, Nagaretani H, Nishizawa H, et al: Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem. 2002, 277 (40): 37487-37491. 10.1074/jbc.M206083200.CrossRefPubMed
8.
Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, et al: Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002, 106 (22): 2767-2770. 10.1161/01.CIR.0000042707.50032.19.CrossRefPubMed
9.
Cai XJ, Li CJ, Chen L, Rong YY, Zhang Y, Zhang M: A hypothesis: adiponectin mediates anti-atherosclerosis via adventitia-AMPK-iNOS pathway. Med Hypotheses. 2008, 70 (5): 1044-1047. 10.1016/j.mehy.2007.08.012.CrossRefPubMed
10.
Tian L, Luo N, Klein RL, Chung BH, Garvey WT, Fu Y: Adiponectin reduces lipid accumulation in macrophage foam cells. Atherosclerosis. 2009, 202 (1): 152-161. 10.1016/j.atherosclerosis.2008.04.011.CrossRefPubMed
11.
Butte NF, Comuzzie AG, Cai G, Cole SA, Mehta NR, Bacino CA: Genetic and environmental factors influencing fasting serum adiponectin in Hispanic children. J Clin Endocrinol Metab. 2005, 90 (7): 4170-4176. 10.1210/jc.2004-2328.CrossRefPubMed
12.
Chuang LM, Chiu YF, Sheu WH, Hung YJ, Ho LT, Grove J, Rodriguez B, Quertermous T, Chen YD, Hsiung CA, et al: Biethnic comparisons of autosomal genomic scan for loci linked to plasma adiponectin in populations of Chinese and Japanese origin. J Clin Endocrinol Metab. 2004, 89 (11): 5772-5778. 10.1210/jc.2004-0640.CrossRefPubMed
13.
Comuzzie AG, Funahashi T, Sonnenberg G, Martin LJ, Jacob HJ, Black AE, Maas D, Takahashi M, Kihara S, Tanaka S, et al: The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J Clin Endocrinol Metab. 2001, 86 (9): 4321-4325. 10.1210/jc.86.9.4321.CrossRefPubMed
14.
Guo X, Saad MF, Langefeld CD, Williams AH, Cui J, Taylor KD, Norris JM, Jinagouda S, Darwin CH, Mitchell BD, et al: Genome-wide linkage of plasma adiponectin reveals a major locus on chromosome 3q distinct from the adiponectin structural gene: the IRAS family study. Diabetes. 2006, 55 (6): 1723-1730. 10.2337/db05-0428.CrossRefPubMed
15.
Pollin TI, Tanner K, O'Connell JR, Ott SH, Damcott CM, Shuldiner AR, McLenithan JC, Mitchell BD: Linkage of plasma adiponectin levels to 3q27 explained by association with variation in the APM1 gene. Diabetes. 2005, 54 (1): 268-274. 10.2337/diabetes.54.1.268.CrossRefPubMed
16.
Tejero ME, Cai G, Goring HH, Diego V, Cole SA, Bacino CA, Butte NF, Comuzzie AG: Linkage analysis of circulating levels of adiponectin in Hispanic children. Int J Obes (Lond). 2007, 31 (3): 535-542. 10.1038/sj.ijo.0803436.CrossRef
17.
Koh KK, Quon MJ, Han SH, Chung WJ, Ahn JY, Seo YH, Choi IS, Shin EK: Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia. J Am Coll Cardiol. 2005, 45 (10): 1649-1653. 10.1016/j.jacc.2005.02.052.CrossRefPubMed
18.
Hiuge A, Tenenbaum A, Maeda N, Benderly M, Kumada M, Fisman EZ, Tanne D, Matas Z, Hibuse T, Fujita K, et al: Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level. Arterioscler Thromb Vasc Biol. 2007, 27 (3): 635-641. 10.1161/01.ATV.0000256469.06782.d5.CrossRefPubMed
19.
Koh KK, Han SH, Quon MJ, Yeal Ahn J, Shin EK: Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia. Diabetes Care. 2005, 28 (6): 1419-1424. 10.2337/diacare.28.6.1419.CrossRefPubMed
20.
Anderlova K, Dolezalova R, Housova J, Bosanska L, Haluzikova D, Kremen J, Skrha J, Haluzik M: Influence of PPAR-alpha agonist fenofibrate on insulin sensitivity and selected adipose tissue-derived hormones in obese women with type 2 diabetes. Physiol Res. 2007, 56 (5): 579-586.PubMed
21.
Oki K, Koide J, Nakanishi S, Nakashima R, Yamane K: Fenofibrate increases high molecular weight adiponectin in subjects with hypertriglyceridemia. Endocr J. 2007, 54 (3): 431-435. 10.1507/endocrj.K06-172.CrossRefPubMed
22.
Lai CQ, Arnett DK, Corella D, Straka RJ, Tsai MY, Peacock JM, Adiconis X, Parnell LD, Hixson JE, Province MA, et al: Fenofibrate effect on triglyceride and postprandial response of apolipoprotein A5 variants: the GOLDN study. Arterioscler Thromb Vasc Biol. 2007, 27 (6): 1417-1425. 10.1161/ATVBAHA.107.140103.CrossRefPubMed
23.
24.
Warodomwichit D, Ordovas J, Shen J, Arnett DK, Tsai MY, Kabagambe EK, Peacock JM, Hixson JE, Straka RJ, Province MA, et al: The genetic variations in the promoter region at adiponectin gene (ADIPOQ) modulate the effect of monounsaturated fatty acid (MUFA) intake on body mass index (BMI) and obesity risk: The Genetics of Lipid Lowering Drugs and Diet Network Study. Obesity (Silver Spring). 2009, 17 (3): 510-517. 10.1038/oby.2008.583.CrossRef
25.
Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G: Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes. 2003, 52 (7): 1779-1785. 10.2337/diabetes.52.7.1779.CrossRefPubMed
26.
Menzaghi C, Trischitta V, Doria A: Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease. Diabetes. 2007, 56 (5): 1198-1209. 10.2337/db06-0506.CrossRefPubMed
27.
Chagnon YC, Perusse L, Lamothe M, Chagnon M, Nadeau A, Dionne FT, Gagnon J, Chung WK, Leibel RL, Bouchard C: Suggestive linkages between markers on human 1p32-p22 and body fat and insulin levels in the Quebec Family Study. Obes Res. 1997, 5 (2): 115-121.CrossRefPubMed
28.
Platte P, Papanicolaou GJ, Johnston J, Klein CM, Doheny KF, Pugh EW, Roy-Gagnon MH, Stunkard AJ, Francomano CA, Wilson AF: A study of linkage and association of body mass index in the Old Order Amish. Am J Med Genet C Semin Med Genet. 2003, 121C (1): 71-80. 10.1002/ajmg.c.20005.CrossRefPubMed
29.
Ehm MG, Karnoub MC, Sakul H, Gottschalk K, Holt DC, Weber JL, Vaske D, Briley D, Briley L, Kopf J, et al: Genomewide search for type 2 diabetes susceptibility genes in four American populations. Am J Hum Genet. 2000, 66 (6): 1871-1881. 10.1086/302950.CrossRefPubMedPubMedCentral
30.
Zhao JY, Xiong MM, Huang W, Wang H, Zuo J, Wu GD, Chen Z, Qiang BQ, Zhang ML, Chen JL, et al: An autosomal genomic scan for loci linked to type 2 diabetes in northern Han Chinese. J Mol Med. 2005, 83 (3): 209-215. 10.1007/s00109-004-0587-3.CrossRefPubMed
31.
Bruun JM, Lihn AS, Verdich C, Pedersen SB, Toubro S, Astrup A, Richelsen B: Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab. 2003, 285 (3): E527-533.CrossRefPubMed
32.
Bernstein EL, Koutkia P, Ljungquist K, Breu J, Canavan B, Grinspoon S: Acute regulation of adiponectin by free fatty acids. Metabolism. 2004, 53 (6): 790-793. 10.1016/j.metabol.2003.12.023.CrossRefPubMed
Metadata
Title
Suggestion for linkage of chromosome 1p35.2 and 3q28 to plasma adiponectin concentrations in the GOLDN Study
Authors
Laura J Rasmussen-Torvik
James S Pankow
James M Peacock
Ingrid B Borecki
James E Hixson
Michael Y Tsai
Edmond K Kabagambe
Donna K Arnett
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2009
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-10-39

Other articles of this Issue 1/2009

BMC Medical Genetics 1/2009 Go to the issue

Research article

Do the mutations of C1GALT1C1gene play important roles in the genetic susceptibility to Chinese IgA nephropathy?

Research article

A mitotic recombination map proximal to the APC locus on chromosome 5q and assessment of influences on colorectal cancer risk

Research article

Use of supplementary phenotype to identify additional rheumatoid arthritis loci in a linkage analysis of 342 UK affected sibling pair families

Research article

Characterisation of CYP2C8, CYP2C9 and CYP2C19 polymorphisms in a Ghanaian population

Research article

Evaluating NAT2PRED for inferring the individual acetylation status from unphased genotype data

Research article

Genetic variation in Fcγ receptor IIa and risk of coronary heart disease: negative results from two large independent populations