Background: Circulating fetuin-A (FetA) inhibits insulin receptor signaling and activates the toll-like receptor 4 proinflammatory cascade; thus, it may contribute to metabolic syndrome. Polymorphisms in alpha-2-Heremans-Schmid glycoprotein (AHSG), the gene which codes FetA, may influence metabolic syndrome progression in higher-risk ethnic groups. We aimed to identify whether individual variation in AHSG influences biomarkers of metabolic disease and obesity in young Mexican adults. Methods: The participants were Mexican college applicants (18-25 years, n = 641). Dietary intake, anthropometric data, and blood for the analysis of biomarkers and genetics were collected. Single nucleotide polymorphisms (SNPs) in AHSG (rs2518136 and rs4917) were genotyped. Results: Neither AHSG SNP was associated with body mass index (BMI) or waist circumference. rs4917 C allele carriers had lower triglycerides (TG) than T allele homozygotes (98.85 ± 2.3 vs. 112.2 ± 5.2 mg/dL, p = 0.0113). BMI was strongly associated with TG (p < 0.0001) regardless of genotype. The relationship between circulating TG and dietary intake of carbohydrates and saturated fat was significant in rs4917 CT allele heterozygotes only (p = 0.03 and p = 0.02, respectively). Conclusions: rs4917 T allele carriers had higher TG. This relationship was exaggerated in individuals with overweight and obesity. Dietary intake was significantly associated with TG in only those with heterozygosity at rs4917, suggesting that these individuals may be more susceptible to dietary interventions.

Must A, Spadano J, Coakley EH, et al: The disease burden associated with overweight and obesity. JAMA 1999;282:1523-1529.
Goustin AS, Abou-Samra AB: The “thrifty” gene encoding Ahsg/fetuin-A meets the insulin receptor: insights into the mechanism of insulin resistance. Cell Signal 2011;23:980-990.
Auberger P, Falquerho L, Contreres JO, et al: Characterization of a natural inhibitor of the insulin receptor tyrosine kinase: cDNA cloning, purification, and anti-mitogenic activity. Cell 1989;58:631-640.
Pal D, Dasgupta S, Kundu R, et al: Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med 2012;18:1279-1285.
Ix JH, Wassel CL, Kanaya AM, et al: Fetuin-A and incident diabetes mellitus in older persons. JAMA 2008;300:182-188.
Jensen MK, Bartz TM, Djousse L, et al: Genetically elevated fetuin-A levels, fasting glucose levels, and risk of type 2 diabetes: the Cardiovascular Health Study. Diabetes Care 2013;36:3121-3127.
Robinson KN, Teran-Garcia M: From infancy to aging: biological and behavioral modifiers of Fetuin-A. Biochimie 2016;124:141-149.
Vionnet N, Hani EH, Dupont S, et al: Genomewide search for type 2 diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21-q24. Am J Hum Genet 2000;67:1470-1480.
Choquette AC, Lemieux S, Tremblay A, et al: Evidence of a quantitative trait locus for energy and macronutrient intakes on chromosome 3q27.3: the Quebec Family Study. Am J Clin Nutr 2008;88:1142-1148.
Andersen G, Burgdorf KS, Sparsø T, et al: AHSG tag single nucleotide polymorphisms associate with type 2 diabetes and dyslipidemia: studies of metabolic traits in 7,683 white Danish subjects. Diabetes 2008;57:1427-1432.
Ix JH, Shlipak MG, Brandenburg VM, et al: Association between human fetuin-A and the metabolic syndrome: data from the Heart and Soul Study. Circulation 2006;113:1760-1767.
Fisher E, Stefan N, Saar K, et al: Association of AHSG gene polymorphisms with fetuin-A plasma levels and cardiovascular diseases in the EPIC-Potsdam study. Circ Cardiovasc Genet 2009;2:607-613.
Dahlman I, Eriksson P, Kaaman M, et al: Alpha2-Heremans-Schmid glycoprotein gene polymorphisms are associated with adipocyte insulin action. Diabetologia 2004;47:1974-1979.
Temesszentandrási G, Vörös K, Böröcz Z, et al: Association of human fetuin-A rs4917 polymorphism with obesity in 2 cohorts. J Investig Med 2015;63:548-553.
Mathews ST, Rakhade S, Zhou X, et al: Fetuin-null mice are protected against obesity and insulin resistance associated with aging. Biochem Biophys Res Commun 2006;350:437-443.
Lavebratt C, Wahlqvist S, Nordfors L, et al: AHSG gene variant is associated with leanness among Swedish men. Hum Genet 2005;117:54-60.
Müssig K, Staiger H, Machicao F, et al: AHSG gene variation is not associated with regional body fat distribution - a magnetic resonance study. Exp Clin Endocrinol Diabetes 2009;117:432-437.
Fesinmeyer MD, Meigs JB, North KE, et al: Genetic variants associated with fasting glucose and insulin concentrations in an ethnically diverse population: results from the Population Architecture using Genomics and Epidemiology (PAGE) study. BMC Med Genet 2013;14:98.
Centers for Disease Control and Prevention: National Diabetes Statistics Report, 2014. Atlanta, Centers for Disease Control and Prevention, 2014.
Ordovas JM, Corella D, Demissie S, et al: Dietary fat intake determines the effect of a common polymorphism in the hepatic lipase gene promoter on high-density lipoprotein metabolism. Circulation 2002;106:2315-2321.
Hernández-Avila M, Romieu I, Parra S, et al: Validity and reproducibility of a food frequency questionnaire to assess dietary intake of women living in Mexico City. Salud Publica Mex 1998;40:133-140.
Romieu I, Hernandez-Avila M, Rivera JA, et al: Dietary studies in countries experiencing a health transition: Mexico and Central America. Am J Clin Nutr 1997;65(4 suppl):1159S-1165S.
Rodríguez-Ramírez S, Mundo-Rosas V, Jiménez-Aguilar A, Shamah-Levy T: Methodology for the analysis of dietary data from the Mexican National Health and Nutrition Survey 2006. Salud Publica Mex 2009;51(suppl 4):S523-S529.
Matthews DR, Hosker JP, Rudenski AS, et al: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-419.
Cooper DN: Functional intronic polymorphisms: buried treasure awaiting discovery within our genes. Hum Genomics 2010;4:284-288.
Kosoy R, Nassir R, Tian C, et al: Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America. Hum Mutat 2009;30:69-78.
Hellerstein MK: Carbohydrate-induced hypertriglyceridemia: modifying factors and implications for cardiovascular risk. Curr Opin Lipidol 2002;13:33-40.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.