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DOI: 10.1055/s-2001-17298
© Johann Ambrosius Barth
Gly15Gly polymorphism within the human adipocyte-specific apM-1gene but not Tyr111His polymorphism is associated with higher levels of cholesterol and LDL-cholesterol in caucasian patients with type 2 diabetes
Publication History
Publication Date:
19 September 2001 (online)
Summary:
The recently described mutations within the human adipocyte-specific apM-1 gene might play a role in the pathogenesis of obesity, type 2 diabetes and related metabolic disorders. Design: Frequency of apM-1 gene polymorphisms and their association with metabolic parameters was evaluated in a population-based sample of 556 type 2 (316 males / 240 females) diabetic patients. PCR-based RFLP analysis was performed in blood samples. The T → G transition at nucleotide +45 within exon-2 [Gly15Gly] was detected with an allelic frequency of 0.91 for the wildtype allele and 0.09 for the mutated allele. The missense point mutation (TAC → CAC) at nucleotide +331 within exon 3 [Tyr111His] was detected with an allelic frequency of 0.97 and 0.03, respectively. These frequencies did not differ from a non-diabetic cohort examined earlier. Concerning the Gly15Gly polymorphism, the TT-genotype was found in 457 (82.2%) and the TG-genotype in 99 (17.8%), concerning the Tyr111His polymorphism, TT-genotype was found in 525 (94.4) and TC-genotype in 31 (5.6%) of type 2 diabetic patients. In TG-genotype as compared to TT-genotype significantly more patients had LDL-serum levels in high LDL-classes (<150 mg/dl: 24.4% (TG) vs. 41.4% (TT), 150mg/dl to 190mg/dl: 40.0% (TG) vs. 33.9% (TT), >190 mg/l: 35.6% (TG) vs. 25.0% (TT); p = 0.010). No differences in serum levels of lipids were found in genotype-subgroups of the Tyr111His polymorphism. Thus, Gly15Gly polymorphism of apM-1 gene might play a role in dyslipidaemia in type 2 diabetic patients.
Key words:
apM-1 - polymorphism - type 2 diabetes - obesity - adipocyte
References
- 1 Arner A. Is familial combined hyperlipidaemia a genetic disorder of adipose tissue?. Curr Opin Lipidol. 8 89-94 1997;
- 2 Barsh G S, Farooqi I S, O'Rahilly S. Genetics of body weight regulation. Nature. 404 644-651 2000;
- 3 Bouchard C, Perusse L, Leblanc C, Tremblay A, Theriault G. Inheritance of the amount and distribution of human body fat. Int J Obesity. 12 201-215 1988;
- 4 Chen D, Garg A. Monogenetic disorders of obesity and body fat distribution. J Lipid Res. 40 1735-1746 1999;
- 5 Choy L N, Rosen B S, Spiegelman B M. Adipsin and an endogenous pathway of complement from adipose cells. J Biol Chem. 267 12736-12741 1992;
- 6 Cianflone K M, Maslowska M H, Sniderman A D. Impaired response of fibroblasts from patients with hyperapobetalipoproteinaemia to acylation stimulating protein. J Clin Invest. 85 722-730 1990;
- 7 Cianflone K, Roncari D A, Maslowska M, Baldo A, Forden J, Sniderman A D. Adipsin/Acylation stimulating protein in human adipocytes: regulation of triacylglcerol synthesis. Biochemistry. 33 9489-9495 1994;
- 8 Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacort J M, Basdevant A, Bougneres P, Lebouc Y, Froguel P, Guy-Grand B. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 392 398-401 1998;
- 9 deGraaf J, Stalenhof A FH. Defects of lipoprotein metabolism in familial combined hyperlipidaemia. Curr Opin Lipidol. 9 189-196 1998;
- 10 Esterbauer H, Krempler F, Oberkofler H, Patsch W. The complement system: a pathway linking host defense and adipocyte biology. Europ J Clin Invest. 29 653-656 1999;
- 11 Friedman J M. Obesity in the new millenium. Nature. 404 632-634 2000;
- 12 He Y, Chen H, Quon M J, Reitman M. The mouse obese Gene. J Biol Chem. 270 28887-28889 1995;
- 13 Hotamisligil G S, Shargill N S, Spiegelman B M. Adipose expression of TNF-α: direct role in obesity-linked insulin resistance. Science. 259 87-91 1993;
- 14 Hotamisligil G S, Spiegelman B . Tumor necrosis factor-α: a key component of the obesity diabetes link. Diabetes. 43 1271-1278 1994;
- 15 Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Matsuzawa Y. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 20 1595-11599 2000;
- 16 Hu E, Liang P, Spiegelman B M. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem. 271 10697-10703 1996;
- 17 Jackson R S, Creemers J W, Ohagi S, Raffin-Sanson M L, Sanders L, Montague C T, Hutton J C, O'Rahilly S. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet. 16 303-306 1997;
- 18 Kopelman P G. Obesity as a medical problem. Nature. 404 635-643 2000;
- 19 Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nature Genetics. 19 155 1998;
- 20 Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose collagen-like factor, apM1. Biochem Biophys Res Commun. 221 286-289 1996;
- 21 Maeda K, Okubo K, Shimomura I, Mizuno K, Matsuzawa Y, Matsubara K. Analysis on an expression profile of genes in the human adipose tissue. Gene. 190 227-235 1997;
- 22 McLean R H, Hoefnagel D. Partial lipodystrophy and familial C3 deficiency. Hum Hered. 30 149-154 1980;
- 23 Montague C T, Farooqi I S, Whitehead J P, Soos M A, Rau H, Wareham N J, Sewter C P, Digby J E, Mohammed S N, Hurst J A, Cheetham C H, Earley A R, Barnett A H, Prins J B, O'Rahilly S. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 387 903-908 1997;
- 24 Peters J M, Barnes R, Bennett L, Gitomer W M, Bowcock A M, Garg A. Localization of the gene for familial partial lipodystrophy (Dunnigan variety) to chromosome 1q21-22. Nat Genet. 18 292-295 1998;
- 25 Puigserver P, Wu Z, Park C W, Graves R, Wright M, Spiegelman B M. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 92 829-839 1998;
- 26 Ristow M, Müller-Wieland D, Pfeiffer A, Krone W, Kahn C R. Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. New Engl J Med. 339 953-959 1998;
- 27 Schäffler A, Langmann T, Palitzsch K D, Schölmerich J, Schmitz G. Identification and characterization of the human adipocyte apM-1 promoter. Biochem Biophys Acta. 1399 187-197 1998;
- 28 Schäffler A, Orsó E, Palitzsch K D, Büchler C, Fürst A, Schölmerich J, Schmitz G. The human apM-1, an adipocyte-specific gene linked to the family of TNF's and to genes expressed in activated T cells, is mapped to chromosome 1q21.3-q23, a susceptibility locus identified for Familial Combined Hyperlipidaemia (FCH). Biochem Biophys Res Commun. 260 416-425 1999;
- 29 Schäffler A, Barth N, Palitzsch K D, Drobnik W, Schölmerich J, Schmitz G. Muation analysis of the human adipocyte-specific apM-1 gene. Europ J Clin Invest. 30 879-887 2000;
- 30 Scherer P E, Williams S, Fogliano M, Baldini G, Lodish H F. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem. 270 26746-26749 1995;
- 31 Shapiro L, Scherer P E. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Current Biology. 8 335-338 1998;
- 32 Shimomura I, Funahashi T, Takahashi M, Maeda K, Kotani K, Nakamura T, Yamashita S, Miura M, Fukuda Y, Takemura K, Tokunaoga K, Matsuzawa Y. Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity. Nature Med. 2 800-803 1996;
- 33 Sniderman A D, Cianflone K. The Adipsin-ASP pathway and regulation of adipocyte function. Ann Med. 26 389-393 1994;
- 34 SPSS Inc .SPSS for Windows 95, V.7.5. SPSS Inc. Chicago 1997
- 35 Strobel A, Issad T, Camoin L, Ozata M, Strosberg A D. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet. 8 213-215 1998;
- 36 Vaisse C, Clement K, Guy-Grand B, Froguel P. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet. 20 113-114 1998;
- 37 White R T, Damm D, Hancock N, Rosen B S, Lowell B B, Usher P, Flier J S, Spiegelman B M. Human Adipsin is identical to complement factor D and is expressed at high levels in adipose tissue. J Biol Chem. 267 9210-9213 1992;
- 38 Yeo G S, Farooqi I S, Aminian S, Halsall D J, Stanhope R G, O'Rahilly S. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet. 20 111-112 1998;
- 39 Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J M. Positional cloning of the mouse obese gene and its human homologue. Nature. 372 425-432 1994;
Bettina ZietzM.D.
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