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

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.

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