Horm Metab Res 2006; 38(11): 773-775
DOI: 10.1055/s-2006-955091
Short Communication

© Georg Thieme Verlag KG Stuttgart · New York

Association Study of the 804C/A and 252A/G Polymorphisms in the Lymphotoxin-α Gene for Microalbuminuria in Japanese Type 2 Diabetic Patients

K. Yoshioka 1 , T. Yoshida 2 , T. Umekawa 2 , Y. Takakura 3 , A. Kogure 3 , H. Toda 4 , T. Yoshikawa 3
  • 1Department of Diabetes and Endocrinology, Matsushita Memorial Hospital, Moriguchi, Japan
  • 2Department of Diabetes and Metabolism, Kyoto City Hospital, Kyoto, Japan
  • 3Department of Endocrinology and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • 4Sakazaki Clinic, Kyoto, Japan
Further Information

Publication History

Received 27 March 2006

Accepted after revision 20 June 2006

Publication Date:
16 November 2006 (online)

Introduction

Inflammatory cytokines tumor necrosis factor-α (TNF-α) and lymphotoxin-α (LTA), previously known as TNF-β, play an inflammatory process in atherosclerosis [1]. These two genes are located closely in tandem within the major histocompatibility complex class III region at chromosome 6p21 [2]. As LTA was expressed in atherosclerotic lesions and absence of LTA reduced the size of these lesions in mice [3], it is possible that LTA may contribute to atherogenesis as a player of vascular inflammation. Recently, the 804C/A and 252A/G polymorphisms in the LTA gene have been identified as a major risk factor for myocardial infarction (MI) in Japanese individuals [4]. Additionally, it has been reported that polymorphism of the LTA gene was associated with the prevalence of type 2 diabetes [5].

Microalbuminuria is known as another independent risk factor for cardiovascular morbidity and mortality in diabetic [6] and nondiabetic subjects [7]. Insulin resistance has been also associated with microalbuminuria [8], to which inflammatory cytokines have been related, thereby contributing to the pathogenic process in albuminuria and nephropathy in diabetes of animal models [9] and humans [10]. Therefore, association study between polymorphism LTA gene and microalbuminuria in diabetes is worth investigating, because such study has not been examined as yet. In this study, we have investigated the relation of the 804C/A and 252A/G polymorphisms in the LTA gene to microalbuminuria in Japanese type 2 diabetic patients.

References

  • 1 Ross R. N Engl J Med. 1999;  340 115-126
  • 2 Campbell RD, Trowsdale J. Immunol Today. 1993;  14 349-352
  • 3 Schreyer SA, Vick CM, LeBoeuf RC. J Biol Chem. 2002;  277 12364-12368
  • 4 Ozaki K, Ohnishi Y, Iida A, Sekine A, Yamada R, Tsunoda T, Sato H, Hori M, Nakamura Y, Tanaka T. Nat Genet. 2002;  32 650-654
  • 5 Yamada A, Ichihara S, Murase Y, Kato T, Izawa H, Nagata K, Murohara T, Yamada Y, Yokota M. J Mol Med. 2004;  82 477-483
  • 6 Schmitz A, Vaeth M. Diab Med. 1984;  5 17-19
  • 7 Mattock MB, Morrish NJ, Viberti GC, Keen H, Fizgerald AP, Jackson G. Diabetes. 1992;  41 736-741
  • 8 Niskanen L, Laakso M. Metabolism. 1993;  42 1541-1545
  • 9 Kalantarinia K, Awad AS, Siragy HM. Kidney Int. 2003;  64 1208-1231
  • 10 Navarro JF, Mora C, Macia M, Garcia J. Am J Kidney Dis. 2003;  42 53-61
  • 11 The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus . Diabetes Care. 2003;  26 ((Suppl 1)) S5-S20
  • 12 Yamada Y, Izawa H, Ichihara S, Takatsu F, Ishihara H, Hirayama H, Sone T, Tanaka M, Yokota M. N Engl J Med. 2002;  347 1916-1923
  • 13 Koch W, Kastrai A, Bottiger C, Mehilli J, von Beckerath N, Schomiq A. Atherosclerosis. 2001;  159 137-144
  • 14 Nakayama T, Soma M, Sato N, Haketa A, Kosuge K, Aoi N, Sato M, Izumi Y, Matsumoto K, Kanmatsuse K, Kokubun S. Am J Hypertens. 2004;  17 1045-1046
  • 15 Messer G, Spengler U, Jung MC, Honold G, Blömer K, Pape GR, Riethmüller G, Weiss E. J Exp Med. 1991;  173 209-219
  • 16 Hayakawa T, Nagai Y, Taniguchi M, Yamashita H, Takamura T, Abe T, Nomura G, Kobayashi K. Metabolism. 2000;  49 1506-1509

Correspondence

Keiji YoshiokaMD 

Department of Diabetes and Endocrinology·Matsushita Memorial Hospital

5-55, Sotojima-cho

Moriguchi

Osaka 570-8540

Japan

Phone: +81/6/6992/12 31

Fax: +81/6/6992/48 45

Email: yoshik@mue.biglobe.ne.jp