Impact of adiponectin gene polymorphisms on plasma lipoprotein and adiponectin concentrations of viscerally obese men

The aim of this study was first to examine the relationships between adiponectin gene (Apm1) polymorphisms and anthropometric indices as well as plasma adiponectin and lipoprotein/lipid levels, and then to investigate whether the presence of visceral obesity or insulin resistance may modulate the impact of these polymorphisms on metabolic risk variables. Molecular screening of the Apm1 gene was achieved, and a sample of 270 unrelated men recruited from the greater Quebec City area and selected to cover a wide range of body fatness values was genotyped. Sequencing of the Apm1 gene revealed two previously reported polymorphisms (c.45T>G and c.276G>T) as well as two newly identified genetic variations (−13752delT and −13702G>C). Carriers of the c.276T allele had higher LDL-cholesterol and lower HDL-triglyceride concentrations than did 276G/G homozygotes (P = 0.02 and P = 0.01, respectively). Carriers of the c.45G allele exhibited higher plasma adiponectin concentrations than did 45T/T homozygotes (P = 0.04). After dividing each genotype group into subgroups for visceral AT, homozygotes for the normal allele at position −13752delT, carriers of the c.45G allele, and carriers of the c.276T allele had similar total apolipoprotein B (apoB) concentrations, whether they were viscerally obese or not.These results suggest that some Apm1 gene polymorphisms influence plasma adiponectin concentrations and lipoprotein/lipid levels. In addition, the impact of these polymorphisms is modulated by the presence of visceral obesity. The aim of this study was first to examine the relationships between adiponectin gene (Apm1) polymorphisms and anthropometric indices as well as plasma adiponectin and lipoprotein/lipid levels, and then to investigate whether the presence of visceral obesity or insulin resistance may modulate the impact of these polymorphisms on metabolic risk variables. Molecular screening of the Apm1 gene was achieved, and a sample of 270 unrelated men recruited from the greater Quebec City area and selected to cover a wide range of body fatness values was genotyped. Sequencing of the Apm1 gene revealed two previously reported polymorphisms (c.45T>G and c.276G>T) as well as two newly identified genetic variations (−13752delT and −13702G>C). Carriers of the c.276T allele had higher LDL-cholesterol and lower HDL-triglyceride concentrations than did 276G/G homozygotes (P = 0.02 and P = 0.01, respectively). Carriers of the c.45G allele exhibited higher plasma adiponectin concentrations than did 45T/T homozygotes (P = 0.04). After dividing each genotype group into subgroups for visceral AT, homozygotes for the normal allele at position −13752delT, carriers of the c.45G allele, and carriers of the c.276T allele had similar total apolipoprotein B (apoB) concentrations, whether they were viscerally obese or not. These results suggest that some Apm1 gene polymorphisms influence plasma adiponectin concentrations and lipoprotein/lipid levels. In addition, the impact of these polymorphisms is modulated by the presence of visceral obesity. Obesity is associated with increased morbidity and mortality (1Allison D.B. Fontaine K.R. Manson J.E. Stevens J. VanItallie T.B. Annual deaths attributable to obesity in the United States.J. Am. Med. Assoc. 1999; 282: 1530-1538Crossref PubMed Scopus (1532) Google Scholar). Obesity, specially the abdominal form, can promote the parallel progression of insulin resistance to type 2 diabetes and endothelial dysfunction to atherosclerosis (2Lyon C.J. Law R.E. Hsueh W.A. Minireview: adiposity, inflammation, and atherogenesis.Endocrinology. 2003; 144: 2195-2200Crossref PubMed Scopus (645) Google Scholar). 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Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity.Intern. Med. 1999; 38: 202-206Crossref PubMed Scopus (292) Google Scholar). Most serum adipocytokine levels have been shown to be increased in obese or insulin-resistant subjects or in subjects with high cardiovascular risk (9Mohamed-Ali V. Goodrick S. Rawesh A. Katz D.R. Miles J.M. Yudkin J.S. Klein S. Coppack S.W. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo.J. Clin. Endocrinol. Metab. 1997; 82: 4196-4200Crossref PubMed Google Scholar, 10Ziccardi P. Nappo F. Giugliano G. Esposito K. Marfella R. Cioffi M. D'Andrea F. Molinari A.M. Giugliano D. Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year.Circulation. 2002; 105: 804-809Crossref PubMed Scopus (818) Google Scholar, 11Samad F. Loskutoff D.J. 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Med. 1999; 38: 202-206Crossref PubMed Scopus (292) Google are associated with insulin abdominal obesity (8Funahashi T. Nakamura T. Shimomura I. Maeda K. Kuriyama H. Takahashi M. Arita Y. Kihara S. Matsuzawa Y. Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity.Intern. Med. 1999; 38: 202-206Crossref PubMed Scopus (292) Google Scholar, C. Funahashi T. S. K. Matsuzawa Y. R.E. in obesity and type 2 with insulin resistance and Clin. Endocrinol. Metab. PubMed Scopus Google and of M. Kihara S. Funahashi T. Nakamura T. H. M. K. Y. H. K. Maeda A. H. H. M. H. T. Matsuzawa Y. Association of with 2003; PubMed Scopus Google Scholar). the of adiponectin is not this is to a the of the metabolic Funahashi T. G. D. Takahashi M. Kihara S. S. Matsuzawa Y. J. D. A. The genetic of plasma in a for obesity and the metabolic Clin. Endocrinol. Metab. PubMed Scopus Google Scholar). is the gene of been on M. Arita Y. K. Y. K. M. Shimomura I. K. Kuriyama H. Kihara S. Nakamura T. S. Funahashi T. Matsuzawa Y. and in J. Metab. 2000; PubMed Scopus Google Scholar). for to the signals in this J. M. K. J. J. on and influence of the metabolic 2000; PubMed Scopus Google Scholar). in 2 of the Apm1 and have been associated with obesity and insulin resistance subjects C. T. R. V. A. at the adiponectin is associated with obesity and of the insulin resistance 2002; PubMed Scopus Google Scholar). have been reported in the in and in and at the of the gene K. P. Y. K. C. K. T. S. T. K. H. R. Y. Y. R. M. K. M. Y. M. S. C. P. T. in the gene adiponectin is associated with an increased risk of type 2 diabetes in the 2002; PubMed Scopus Google Scholar, F. C. S. V. S. P. M. F. S. K. K. B. T. P. in the and of the gene modulate adiponectin levels and to the genetic risk for type 2 diabetes in 2002; 11: PubMed Scopus Google Scholar). The aim of this study was first to genetic variations in the Apm1 gene in subjects with high levels of visceral and then to the impact of these on two anthropometric plasma adiponectin concentrations and plasma lipoprotein/lipid levels. to investigate whether the presence of visceral obesity or insulin resistance may modulate the The Apm1 gene was first in subjects low visceral and subjects with high visceral a was a sample of 270 unrelated from the greater City area and selected to cover a wide range of body fatness was genotyped. These men were and from metabolic as type 2 and C. Prud'homme D. Nadeau A. J. Tremblay A. J.P. M.C. of the on triglyceride metabolism of viscerally obese PubMed Scopus Google Scholar). of was to insulin or plasma lipoprotein levels. subjects to into this was by the of body and were to K. for the of visceral a J. Metab. Google Scholar). Visceral area at the was by on a as previously J.P. Prud'homme D. M.C. Tremblay A. Bouchard C. of abdominal from anthropometric in J. Clin. PubMed Scopus Google Scholar, M. Després J.P. Tremblay A. S. Nadeau A. Moorjani S. Lupien P.J. G. Bouchard C. of adipose tissue distribution by in obese with body and anthropometric J. PubMed Scopus Google Scholar). and triglyceride concentrations were on a were by and the was after of LDL in the with and S. A. Labrie F. Lupien P.J. D. C. M. A. in plasma lipoprotein in men with Full Text PDF PubMed Scopus Google Scholar). concentrations were in plasma and by the of of by in as previously S. A. Labrie F. Lupien P.J. D. C. M. A. in plasma lipoprotein in men with Full Text PDF PubMed Scopus Google Scholar). were in from the for had been and at After an were in through a in an for the of plasma insulin concentrations R. H. Med. Google Scholar). insulin levels were by with B. of to in Clin. Endocrinol. Metab. 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M. K. F. J. M. A.M. Association between adiponectin and of in obese 2003; PubMed Scopus Google each genotype group was into subgroups a of for insulin concentrations to insulin-resistant subjects from men with a normal insulin Carriers of the allele with high insulin levels had lower adiponectin concentrations than subjects with low insulin levels. In similar adiponectin concentrations were for homozygotes the at position characterized by high or low insulin The adiponectin gene a that M. M. Maeda Funahashi T. Matsuzawa Y. M. Shimomura I. of a and by 2003; PubMed Scopus Google Scholar). whether an between the and adiponectin polymorphisms modulate lipoprotein/lipid concentrations and anthropometric was not The of the adiponectin and of gene Apm1 is in the of the of obesity H. J. C. A. F. M. of serum adiponectin and concentrations with body distribution in 2003; 11: PubMed Scopus Google type 2 diabetes C. Funahashi T. S. K. Matsuzawa Y. R.E. in obesity and type 2 with insulin resistance and Clin. Endocrinol. Metab. PubMed Scopus Google Scholar, M. S. S. plasma adiponectin concentrations in women with Clin. Endocrinol. Metab. 2002; PubMed Scopus Google Scholar, K. H. H. H. S. Maeda A. T. K. M. H. Y. Maeda K. Kihara S. Funahashi T. Matsuzawa Y. of adiponectin associated with the metabolic 2003; PubMed Scopus Google and cardiovascular risk M. S. S. plasma adiponectin concentrations in women with Clin. Endocrinol. Metab. 2002; PubMed Scopus Google Scholar, M. Kihara S. S. T. S. Arita Y. Y. Shimomura I. H. Nakamura T. Funahashi T. Matsuzawa Y. Association of with in 2003; PubMed Scopus Google Scholar). The first of this study was to polymorphisms in the Apm1 gene in a sample of men for low or high visceral in the Apm1 gene were of and were similar to previously reported in C. T. R. V. A. at the adiponectin is associated with obesity and of the insulin resistance 2002; PubMed Scopus Google Scholar, F. C. S. V. S. P. M. F. S. K. K. B. T. P. in the and of the gene modulate adiponectin levels and to the genetic risk for type 2 diabetes in 2002; 11: PubMed Scopus Google Scholar). However, the of the was higher in a K. P. Y. K. C. K. T. S. T. K. H. R. Y. Y. R. M. K. M. Y. M. S. C. P. T. in the gene adiponectin is associated with an increased risk of type 2 diabetes in the 2002; PubMed Scopus Google as by F. C. S. V. S. P. M. F. S. K. K. B. T. P. in the and of the gene modulate adiponectin levels and to the genetic risk for type 2 diabetes in 2002; 11: PubMed Scopus Google Scholar). may be attributable to the of the In the some of Apm1 polymorphisms with obesity higher LDL-cholesterol and lower HDL-triglyceride levels were in carriers of the allele These suggest an of the allele may be from a cardiovascular than the c.276T is a have the impact on lipoprotein/lipid may be in with polymorphisms in that and in levels M. A. H. M. F. H. Association of the in adiponectin with obesity and insulin with of type 2 2002; PubMed Scopus Google or be in with a gene that plasma lipoprotein levels. plasma adiponectin levels have been reported in at high risk of cardiovascular Kihara S. Arita Y. M. A. Y. M. Kuriyama H. K. H. K. M. Y. S. Funahashi T. Matsuzawa Y. plasma and expression in PubMed Scopus Google Scholar). between the genotype and adiponectin levels been obese subjects K. P. Y. K. C. K. T. S. T. K. H. R. Y. Y. R. M. K. M. Y. M. S. C. P. T. in the gene adiponectin is associated with an increased risk of type 2 diabetes in the 2002; PubMed Scopus Google Scholar). did not a in may be attributable to the of the study to the of F. C. S. V. S. P. M. F. S. K. K. B. T. P. in the and of the gene modulate adiponectin levels and to the genetic risk for type 2 diabetes in 2002; 11: PubMed Scopus Google Scholar) in a 45T/T homozygotes had lower plasma adiponectin levels with carriers of the of adiponectin been associated with a high risk of in obesity (8Funahashi T. Nakamura T. Shimomura I. Maeda K. Kuriyama H. Takahashi M. Arita Y. Kihara S. Matsuzawa Y. Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity.Intern. Med. 1999; 38: 202-206Crossref PubMed Scopus (292) Google Scholar, A. A. Gomez-Ambrosi J. G. J. Adipose tissue as an endocrine of and adiponectin in the pathogenesis of cardiovascular Physiol. 2003; PubMed Scopus Google Scholar). been previously reported that plasma concentrations of adiponectin are lower obese than subjects (13Arita Y. Kihar S. Funahashi T. Takahashi M. S. Maeda K. is decreased in obesity and J. Scholar, T. A. T. G. adiponectin is associated with lipoprotein and lipoprotein in Full Text Full Text PDF PubMed Scopus Google Scholar). After dividing the two genotype into subgroups as a for visceral AT, a of obesity and genotype was for plasma adiponectin concentrations In addition, a (P = increased plasma adiponectin levels in carriers of c.276T was with obese the presence of obesity was associated with adiponectin concentrations (13Arita Y. Kihar S. Funahashi T. Takahashi M. S. Maeda K. is decreased in obesity and J. Scholar, H. J. C. A. F. M. of serum adiponectin and concentrations with body distribution in 2003; 11: PubMed Scopus Google Scholar, P. is a gene in 1996; Full Text Full Text PDF PubMed Scopus Google the and to be than the and K. P. Y. K. C. K. T. S. T. K. H. R. Y. Y. R. M. K. M. Y. M. S. C. P. T. in the gene adiponectin is associated with an increased risk of type 2 diabetes in the 2002; PubMed Scopus Google Scholar) a similar of the genotype on plasma adiponectin concentrations after dividing study sample of and normal men and women on the of and of body P. Bouchard C. in the adiponectin gene in and obese subjects from the 2003; Full Text Full Text PDF PubMed Scopus Google Scholar) that obese women the allele were higher plasma and than obese women for The presence of visceral modulated the of −13752delT, and gene to in plasma total levels. carriers of the c.45G allele, carriers of c.276T allele and for normal allele at position total concentrations were in obese to men. However, concentrations similar in carriers of allele, 45T/T homozygotes as well as 276G/G homozygotes of of visceral The that and as well as and were in may the similar results for these genetic variations the between and abdominal obesity, to this in an study sample of unrelated from the in the of the of Quebec J. C. A. S. A. D. M.C. Association between the and of the metabolic PubMed Scopus Google Scholar). The of the allele in the sample was similar to the in the sample of men from the greater Quebec area visceral by was not for subjects from the subjects in on the of first and on the of genotype and plasma results were in with the total concentrations in carriers of the After for and adiponectin concentrations, for total levels were for the and (P = and P = respectively). M. P.J. D.B. of adiponectin to body insulin and plasma for of and 2003; PubMed Scopus Google Scholar) to a between adiponectin concentrations and levels. adiponectin concentrations in with were lower than in subjects and with Y. K. D. Y. S. M. T. K. S. Y. M. K. J. of plasma concentrations of adiponectin in with PubMed Scopus Google Scholar). T. A. T. G. adiponectin is associated with lipoprotein and lipoprotein in Full Text Full Text PDF PubMed Scopus Google Scholar) an between adiponectin and after for in men. However, plasma adiponectin concentrations were with visceral AT, but carriers of the allele 2 = P = 2 = P = 45T/T In the presence of the genotype the impact of obesity on total levels. impact may be by adiponectin concentrations in carriers of the These results in plasma adiponectin concentrations have been associated with insulin C. Funahashi T. S. K. Matsuzawa Y. R.E. in obesity and type 2 with insulin resistance and Clin. Endocrinol. Metab. PubMed Scopus Google Scholar, A. C. M. F. S. H. H. M. adiponectin concentrations insulin of glucose and 2003; PubMed Scopus Google whether insulin plasma levels modulate the of each on plasma adiponectin The insulin levels carriers of the allele the concentrations of adiponectin with the insulin levels The of in subjects may be as in that adiponectin concentrations were by the in insulin levels this was in with the allele, to in adiponectin concentrations for this These results be by the adiponectin gene a for the of the of the genotype and adiponectin polymorphisms on anthropometric and variables. did modulate adiponectin concentrations in a Y. H. K. K. I. M. M. T. gene may influence serum of an in the 2002; Full Text PDF PubMed Scopus Google C. F. A. M. H. influence of the genotype on serum adiponectin concentrations in 2003; Full Text Full Text PDF PubMed Scopus Google Scholar) influence of the on serum adiponectin concentrations in similar to in the study not to on plasma lipoprotein/lipid levels, and anthropometric In some polymorphisms of the Apm1 gene in this study may to the variations in plasma lipoprotein and adiponectin concentrations men. The presence of visceral obesity or insulin resistance may modulate these These results in and The are to the subjects in this is the of a from the is a from the is a of and of by and M.C. and are the of from and from the of and of by and of this was by the for and the and of

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