Skip to main content
Erschienen in: International Urology and Nephrology 6/2012

01.12.2012 | Nephrology – Original Paper

Association of 276G>T adiponectin gene polymorphism to plasma adiponectin and albuminuria in type 2 diabetic patients

verfasst von: Ina Maria Kacso, Adrian Pavel Trifa, Radu Anghel Popp, Gabriel Kacso

Erschienen in: International Urology and Nephrology | Ausgabe 6/2012

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The 276G>T polymorphism of the adiponectin (ADIPOQ) gene has been correlated with plasma adiponectin, type 2 diabetes (T2D) and its complications. Studies of the role of 276G>T polymorphism in the prevalence of T2D kidney disease are few and contradictory; ethnic differences might play a role. We aimed to assess the relationship of this polymorphism with albuminuria in a cohort of Caucasian T2D patients.

Methods

Consecutive T2D outclinic patients were screened and included upon informed consent; exclusion criteria were glomerular filtration rate (GFR) <30 ml/min, acute intercurrent illness and urinary tract infection. History, standard laboratory evaluation, total plasma adiponectin and genotyping for the 276 ADIPOQ locus were obtained.

Results

One hundred and three T2D patients were included. Forty-three (41.7%) of them had GG genotype, 50 (48.5%) had GT and 10 (9.7%) had TT genotype. Plasma adiponectin was significantly higher in TT-allele carriers (19.03 ± 3.46 μg/ml) than in GT (10.14 ± 1.78 μg/ml) and GG carriers (8.71 ± 1.60 μg/ml), P = 0.003. Adiponectin was higher in albuminuric (13.97 ± 2.07 μg/ml) than in normoalbuminuric patients (6.91 ± 0.88 μg/ml), P = 0.004. The prevalence of T allele was higher in normoalbuminuric patients [36 (69.2%) GT + TT carriers] than in albuminuric ones [24 (47.1%)], P = 0.02. Logistic regression identified the following as predictors of albuminuria: GG genotype: P = 0.003 (OR 4.2; CI 1.61–10.96); low GFR: P = 0.003 (OR 0.97; CI 0.95–0.99); and high plasma adiponectin: P = 0.012 (OR 1.07; CI 1.01–1.14).

Conclusions

Our data suggest that 276G>T polymorphism of the ADIPOQ gene is associated with plasma adiponectin levels. By influencing adiponectinemia, 276G>T polymorphism might predict the presence of albuminuria in Caucasian T2D patients.
Literatur
1.
Zurück zum Zitat Hopkins TA, Ouchi N, Shibata R et al (2007) Adiponectin actions in the cardiovascular system. Cardiovasc Res 74(1):11–18PubMedCrossRef Hopkins TA, Ouchi N, Shibata R et al (2007) Adiponectin actions in the cardiovascular system. Cardiovasc Res 74(1):11–18PubMedCrossRef
2.
Zurück zum Zitat Vasseur F, Helbecque N, Dina C et al (2002) Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet 11(21):2607–2614PubMedCrossRef Vasseur F, Helbecque N, Dina C et al (2002) Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet 11(21):2607–2614PubMedCrossRef
3.
Zurück zum Zitat Qi L, Li T, Rimm E, Zhang C et al (2005) The +276 polymorphism of the APM1 gene, plasma adiponectin concentration, and cardiovascular risk in diabetic men. Diabetes 54(5):1607–1610PubMedCrossRef Qi L, Li T, Rimm E, Zhang C et al (2005) The +276 polymorphism of the APM1 gene, plasma adiponectin concentration, and cardiovascular risk in diabetic men. Diabetes 54(5):1607–1610PubMedCrossRef
4.
Zurück zum Zitat Pollin TI, Tanner K, O’Connell JR et al (2005) Linkage of plasma Adiponectin levels to 3q27 explained by association with variation in the APM1 Gene. Diabetes 54(1):268–274PubMedCrossRef Pollin TI, Tanner K, O’Connell JR et al (2005) Linkage of plasma Adiponectin levels to 3q27 explained by association with variation in the APM1 Gene. Diabetes 54(1):268–274PubMedCrossRef
5.
Zurück zum Zitat Hara K, Boutin P, Mori Y et al (2002) Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 51(2):536–540PubMedCrossRef Hara K, Boutin P, Mori Y et al (2002) Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 51(2):536–540PubMedCrossRef
6.
Zurück zum Zitat Szopa M, Malczewska-Malec M, Kiec-Wilk B et al (2009) Variants of the adiponectin gene and type 2 diabetes in a Polish population. Acta Diabetol 46(4):317–322PubMedCrossRef Szopa M, Malczewska-Malec M, Kiec-Wilk B et al (2009) Variants of the adiponectin gene and type 2 diabetes in a Polish population. Acta Diabetol 46(4):317–322PubMedCrossRef
7.
Zurück zum Zitat Menzaghi C, Ercolino T, Di Paola R et al (2002) A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes 51(7):2306–2312PubMedCrossRef Menzaghi C, Ercolino T, Di Paola R et al (2002) A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes 51(7):2306–2312PubMedCrossRef
8.
Zurück zum Zitat Ohashi K, Iwatani H, Kihara S et al (2007) Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice. Arterioscler Thromb Vasc Biol 27(9):1910–1917PubMedCrossRef Ohashi K, Iwatani H, Kihara S et al (2007) Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice. Arterioscler Thromb Vasc Biol 27(9):1910–1917PubMedCrossRef
9.
Zurück zum Zitat Sharma K, Ramachandrarao S, Qiu G et al (2008) Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest 118(5):1645–1656PubMed Sharma K, Ramachandrarao S, Qiu G et al (2008) Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest 118(5):1645–1656PubMed
10.
Zurück zum Zitat Zhang N, Shi YH, Hao CF et al (2008) Association of +45G15G(T/G) and +276(G/T) polymorphisms in the ADIPOQ gene with polycystic ovary syndrome among Han Chinese women. Eur J Endocrinol 158(2):255–260PubMedCrossRef Zhang N, Shi YH, Hao CF et al (2008) Association of +45G15G(T/G) and +276(G/T) polymorphisms in the ADIPOQ gene with polycystic ovary syndrome among Han Chinese women. Eur J Endocrinol 158(2):255–260PubMedCrossRef
11.
Zurück zum Zitat Krízová J, Dolinková M, Lacinová Z et al (2008) Adiponectin and resistin gene polymorphisms in patients with anorexia nervosa and obesity and its influence on metabolic phenotype. Physiol Res 57(4):539–546PubMed Krízová J, Dolinková M, Lacinová Z et al (2008) Adiponectin and resistin gene polymorphisms in patients with anorexia nervosa and obesity and its influence on metabolic phenotype. Physiol Res 57(4):539–546PubMed
12.
Zurück zum Zitat Lee YY, Lee NS, Cho YM et al (2005) Genetic association study of adiponectin polymorphisms with risk of Type 2 diabetes mellitus in Korean population. Diabet Med 22(5):569–575PubMedCrossRef Lee YY, Lee NS, Cho YM et al (2005) Genetic association study of adiponectin polymorphisms with risk of Type 2 diabetes mellitus in Korean population. Diabet Med 22(5):569–575PubMedCrossRef
13.
Zurück zum Zitat Schalkwijk CG, Chatuverdi N, Schram MT et al (2006) Adiponectin is inversely associated with renal function in type 1 diabetic patients. J Clin Endocrinol Metab 91(1):129–135PubMedCrossRef Schalkwijk CG, Chatuverdi N, Schram MT et al (2006) Adiponectin is inversely associated with renal function in type 1 diabetic patients. J Clin Endocrinol Metab 91(1):129–135PubMedCrossRef
14.
Zurück zum Zitat Komaba H, Igaki N, Goto S et al (2006) Increased serum high-molecular-weight complex of adiponectin in type 2 diabetic patients with impaired renal function. Am J Nephrol 26(5):476–482PubMedCrossRef Komaba H, Igaki N, Goto S et al (2006) Increased serum high-molecular-weight complex of adiponectin in type 2 diabetic patients with impaired renal function. Am J Nephrol 26(5):476–482PubMedCrossRef
15.
Zurück zum Zitat Saraheimo M, Forsblom C, Thorn L et al (2005) Serum adiponectin is increased in type 1 diabetic patients with nephropathy. Diabetes Care 28(6):1410–1414PubMedCrossRef Saraheimo M, Forsblom C, Thorn L et al (2005) Serum adiponectin is increased in type 1 diabetic patients with nephropathy. Diabetes Care 28(6):1410–1414PubMedCrossRef
16.
Zurück zum Zitat Shimotomai T, Kakei M, Narita T et al (2005) Enhanced urinary adiponectin excretion in IgA-nephropathy patients with proteinuria. Ren Fail 27(3):323–328PubMed Shimotomai T, Kakei M, Narita T et al (2005) Enhanced urinary adiponectin excretion in IgA-nephropathy patients with proteinuria. Ren Fail 27(3):323–328PubMed
17.
Zurück zum Zitat Oguz Y, Yilmaz MI, Acikel C et al (2009) The relationship between adiponectin levels and degree of proteinuria in patients with nephrotic and nonnephrotic proteinuria. Ren Fail 31(1):29–35PubMedCrossRef Oguz Y, Yilmaz MI, Acikel C et al (2009) The relationship between adiponectin levels and degree of proteinuria in patients with nephrotic and nonnephrotic proteinuria. Ren Fail 31(1):29–35PubMedCrossRef
18.
Zurück zum Zitat Lin J, Hu FB, Curhan G (2007) Serum adiponectin and renal dysfunction in men with type 2 diabetes. Diabetes Care 30(2):239–244PubMedCrossRef Lin J, Hu FB, Curhan G (2007) Serum adiponectin and renal dysfunction in men with type 2 diabetes. Diabetes Care 30(2):239–244PubMedCrossRef
19.
Zurück zum Zitat Kacso I, Lenghel A, Bondor CI et al (2011) Low plasma adiponectin levels predict increased urinary albumin/creatinine ratio in type 2 diabetes patients. Int Urol Nephrol 2011 Oct 13 [Epub ahead of print] Kacso I, Lenghel A, Bondor CI et al (2011) Low plasma adiponectin levels predict increased urinary albumin/creatinine ratio in type 2 diabetes patients. Int Urol Nephrol 2011 Oct 13 [Epub ahead of print]
20.
Zurück zum Zitat Kollerits B, Fliser D, Heid IM et al (2007) Gender-specific association of adiponectin as a predictor of progression of chronic kidney disease: the mild to moderate kidney disease study. Kidney Int 71(12):1279–1286PubMedCrossRef Kollerits B, Fliser D, Heid IM et al (2007) Gender-specific association of adiponectin as a predictor of progression of chronic kidney disease: the mild to moderate kidney disease study. Kidney Int 71(12):1279–1286PubMedCrossRef
21.
Zurück zum Zitat Jorsal A, Tarnow L, Frystyk J, Lajer M, Flyvbjerg A, Parving HH et al (2008) Serum adiponectin predicts all-cause mortality and end stage renal disease in patients with type I diabetes and diabetic nephropathy. Kidney Int 74(5):649–654PubMedCrossRef Jorsal A, Tarnow L, Frystyk J, Lajer M, Flyvbjerg A, Parving HH et al (2008) Serum adiponectin predicts all-cause mortality and end stage renal disease in patients with type I diabetes and diabetic nephropathy. Kidney Int 74(5):649–654PubMedCrossRef
22.
Zurück zum Zitat Menon V, Li L, Wang X et al (2009) Adiponectin and mortality in patients with chronic kidney disease. J Am Soc Nephrol 17(9):2599–2606CrossRef Menon V, Li L, Wang X et al (2009) Adiponectin and mortality in patients with chronic kidney disease. J Am Soc Nephrol 17(9):2599–2606CrossRef
23.
Zurück zum Zitat Bostrom MA, Freedman BI, Langefeld CD et al (2009) Association of adiponectin gene polymorphisms with type 2 diabetes in an African American population enriched for nephropathy. Diabetes 58(2):499–504PubMedCrossRef Bostrom MA, Freedman BI, Langefeld CD et al (2009) Association of adiponectin gene polymorphisms with type 2 diabetes in an African American population enriched for nephropathy. Diabetes 58(2):499–504PubMedCrossRef
24.
Zurück zum Zitat Yoshioka K, Yoshida T, Umekawa T et al (2004) Adiponectin gene polymorphism (G276T) is not associated with incipient diabetic nephropathy in Japanese type 2 diabetic patients. Metabolism 53(9):1223–1226PubMedCrossRef Yoshioka K, Yoshida T, Umekawa T et al (2004) Adiponectin gene polymorphism (G276T) is not associated with incipient diabetic nephropathy in Japanese type 2 diabetic patients. Metabolism 53(9):1223–1226PubMedCrossRef
25.
Zurück zum Zitat Jaziri R, Aubert R, Roussel R et al (2010) Association of ADIPOQ genetic variants and plasma adiponectin isoforms with the risk of incident renal events in type 2 diabetes. Nephrol Dial Transplant 25(7):2231–2237PubMedCrossRef Jaziri R, Aubert R, Roussel R et al (2010) Association of ADIPOQ genetic variants and plasma adiponectin isoforms with the risk of incident renal events in type 2 diabetes. Nephrol Dial Transplant 25(7):2231–2237PubMedCrossRef
26.
Zurück zum Zitat Ouedraogo R, Gong Y, Berzins B et al (2007) Adiponectin deficiency increases leukocyte endothelium interactions via upregulation of endothelial cell adhesion molecules in vivo. J Clin Invest 117(6):1718–1726PubMedCrossRef Ouedraogo R, Gong Y, Berzins B et al (2007) Adiponectin deficiency increases leukocyte endothelium interactions via upregulation of endothelial cell adhesion molecules in vivo. J Clin Invest 117(6):1718–1726PubMedCrossRef
27.
Zurück zum Zitat Nakamaki S, Satoh H, Kudoh A (2011) Adiponectin reduces proteinuria in streptozotocin-induced diabetic Wistar rats. Exp Biol Med (Maywood) 236(5):614–620CrossRef Nakamaki S, Satoh H, Kudoh A (2011) Adiponectin reduces proteinuria in streptozotocin-induced diabetic Wistar rats. Exp Biol Med (Maywood) 236(5):614–620CrossRef
28.
Zurück zum Zitat Yilmaz MI, Saglam M, Qureshi AR et al (2008) Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin. Nephrol Dial Transplant 23(5):1621–1627PubMedCrossRef Yilmaz MI, Saglam M, Qureshi AR et al (2008) Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin. Nephrol Dial Transplant 23(5):1621–1627PubMedCrossRef
29.
Zurück zum Zitat Ran J, Xiong X, Liu W et al (2010) Increased plasma adiponectin closely associates with vascular endothelial dysfunction in type 2 diabetic patients with diabetic nephropathy. Diab Res Clin Pract 88(2):177–183CrossRef Ran J, Xiong X, Liu W et al (2010) Increased plasma adiponectin closely associates with vascular endothelial dysfunction in type 2 diabetic patients with diabetic nephropathy. Diab Res Clin Pract 88(2):177–183CrossRef
30.
Zurück zum Zitat Lenghel AR, Kacso IM, Bondor CI et al (2011). Intercellular adhesion molecule, plasma adiponectin and albuminuria in type 2 diabetic patients. Diab Res Clin Pract Sep 24 [Epub ahead of print] Lenghel AR, Kacso IM, Bondor CI et al (2011). Intercellular adhesion molecule, plasma adiponectin and albuminuria in type 2 diabetic patients. Diab Res Clin Pract Sep 24 [Epub ahead of print]
31.
Zurück zum Zitat Kelly DJ, Zhang Y, Hepper C et al (2003) Protein kinase C inhibition attenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension. Diabetes 52(2):512–518PubMedCrossRef Kelly DJ, Zhang Y, Hepper C et al (2003) Protein kinase C inhibition attenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension. Diabetes 52(2):512–518PubMedCrossRef
32.
Zurück zum Zitat Tuttle KR, Anderson PW (2003) A novel potential therapy for diabetic nephropathy and vascular complications: protein kinase C beta inhibition. Am J Kidney Dis 42(3):456–465PubMedCrossRef Tuttle KR, Anderson PW (2003) A novel potential therapy for diabetic nephropathy and vascular complications: protein kinase C beta inhibition. Am J Kidney Dis 42(3):456–465PubMedCrossRef
33.
Zurück zum Zitat Tuttle KR, Bakris GL, Toto RD et al (2005) The effect of ruboxistaurin on nephropathy in type 2 diabetes. Diabetes Care 28(11):2686–2690PubMedCrossRef Tuttle KR, Bakris GL, Toto RD et al (2005) The effect of ruboxistaurin on nephropathy in type 2 diabetes. Diabetes Care 28(11):2686–2690PubMedCrossRef
34.
Zurück zum Zitat Tuttle KR, McGill JB, Hayney DJ et al, for the PKC-DRS, PKC-DMES, and PKC-DRS 2 Study Groups (2007). Kidney outcomes in long-term studies of ruboxistaurin for diabetic eye disease. Clin J Am Soc Nephrol 2(4):631–636 Tuttle KR, McGill JB, Hayney DJ et al, for the PKC-DRS, PKC-DMES, and PKC-DRS 2 Study Groups (2007). Kidney outcomes in long-term studies of ruboxistaurin for diabetic eye disease. Clin J Am Soc Nephrol 2(4):631–636
35.
Zurück zum Zitat Forbes JM, Thallas V, Thomas M et al (2003) The breakdown of pre-existing advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes. FASEB J 17(12):1762–1764PubMed Forbes JM, Thallas V, Thomas M et al (2003) The breakdown of pre-existing advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes. FASEB J 17(12):1762–1764PubMed
36.
Zurück zum Zitat Coughlan MT, Forbes JM, Cooper ME (2007) Role of the AGE crosslink breaker, alagebrium, as a renoprotective agent in diabetes. Kidney Int Suppl 106:54–60CrossRef Coughlan MT, Forbes JM, Cooper ME (2007) Role of the AGE crosslink breaker, alagebrium, as a renoprotective agent in diabetes. Kidney Int Suppl 106:54–60CrossRef
37.
Zurück zum Zitat Donnelly SM, Zhou XP, Huang JT et al (1996) Prevention of early glomerulopathy with tolrestat in the streptozotocin-induced diabetic rat. Biochem Cell Biol 74(3):355–362PubMedCrossRef Donnelly SM, Zhou XP, Huang JT et al (1996) Prevention of early glomerulopathy with tolrestat in the streptozotocin-induced diabetic rat. Biochem Cell Biol 74(3):355–362PubMedCrossRef
38.
Zurück zum Zitat Itagaki I, Shimizu K, Kamanaka Y et al (1994) The effect of an aldose reductase inhibitor (Epalrestat) on diabetic nephropathy in rats. Diabetes Res Clin Pract 25(3):147–154PubMedCrossRef Itagaki I, Shimizu K, Kamanaka Y et al (1994) The effect of an aldose reductase inhibitor (Epalrestat) on diabetic nephropathy in rats. Diabetes Res Clin Pract 25(3):147–154PubMedCrossRef
39.
Zurück zum Zitat Passariello N, Sepe J, Marrazzo G et al (1993) Effect of aldose reductase inhibitor (tolrestat) on urinary albumin excretion rate and glomerular filtration rate in IDDM subjects with nephropathy. Diabetes Care 16(5):789–795PubMedCrossRef Passariello N, Sepe J, Marrazzo G et al (1993) Effect of aldose reductase inhibitor (tolrestat) on urinary albumin excretion rate and glomerular filtration rate in IDDM subjects with nephropathy. Diabetes Care 16(5):789–795PubMedCrossRef
40.
Zurück zum Zitat Iso K, Tada H, Kuboki K et al (2001) Long-term effect of epalrestat, an aldose reductase inhibitor, on the development of incipient diabetic nephropathy in Type 2 diabetic patients. J Diabetes Complications 15(5):241–244PubMedCrossRef Iso K, Tada H, Kuboki K et al (2001) Long-term effect of epalrestat, an aldose reductase inhibitor, on the development of incipient diabetic nephropathy in Type 2 diabetic patients. J Diabetes Complications 15(5):241–244PubMedCrossRef
41.
Zurück zum Zitat Ranganathan S, Krempf M, Feraille E et al (1993) Short term effect of an aldose reductase inhibitor on urinary albumin excretion rate (UAER) and glomerular filtration rate (GFR) in type 1 diabetic patients with incipient nephropathy. Diabete Metab 19(2):257–261PubMed Ranganathan S, Krempf M, Feraille E et al (1993) Short term effect of an aldose reductase inhibitor on urinary albumin excretion rate (UAER) and glomerular filtration rate (GFR) in type 1 diabetic patients with incipient nephropathy. Diabete Metab 19(2):257–261PubMed
Metadaten
Titel
Association of 276G>T adiponectin gene polymorphism to plasma adiponectin and albuminuria in type 2 diabetic patients
verfasst von
Ina Maria Kacso
Adrian Pavel Trifa
Radu Anghel Popp
Gabriel Kacso
Publikationsdatum
01.12.2012
Verlag
Springer Netherlands
Erschienen in
International Urology and Nephrology / Ausgabe 6/2012
Print ISSN: 0301-1623
Elektronische ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-011-0118-4

Weitere Artikel der Ausgabe 6/2012

International Urology and Nephrology 6/2012 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Semaglutid bei Herzinsuffizienz: Wie erklärt sich die Wirksamkeit?

17.05.2024 Herzinsuffizienz Nachrichten

Bei adipösen Patienten mit Herzinsuffizienz des HFpEF-Phänotyps ist Semaglutid von symptomatischem Nutzen. Resultiert dieser Benefit allein aus der Gewichtsreduktion oder auch aus spezifischen Effekten auf die Herzinsuffizienz-Pathogenese? Eine neue Analyse gibt Aufschluss.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.