Cytokine gene polymorphisms: Can these differentiate renal disease entities?

Immunoglobulin A (IgA) nephropathy (IgAN) is one of the most common causes of primary glomerulonephritis (GN), and shows diverse clinical presentations, leading to progressive renal failure in some patients [1]. The etiology of IgAN is considered to be multifactorial [2]. The genetic factors may influence disease susceptibility and the likelihood of the disease progressing to end-stage renal disease. Evidence for a genetic contribution has come from the observation that some families are affected in an apparently autosomal dominant fashion, although this is not common [3–5]. Furthermore, ethnicity seems to influence susceptibility to the disease and impacts upon disease progression. The prevalence of IgAN varies among racial groups, as is most common among Asians and American Indians, intermediate in Hispanics and Caucasians, and rare in African and American blacks. In addition to the genetic determinants of disease susceptibility, there are genetic associations with the tendency for IgAN to progress. The analyses of the genetic polymorphisms of several cytokines and chemokines have been widely performed for the elucidation of genetic determinants of IgAN regarding susceptibility and progression. Thin basement membrane nephropathy (TBMN) is one of the most common causes of persistent hematuria in children and adults, the other main etiologies being Alport's syndrome and IgAN [6,7]. Besides hematuria, patients with TBMN usually have minimal proteinuria, normal renal function, and uniformly thinned glomerular basement membranes (GBMs), as determined by electron microscopy [8]. In some patients, microscopic hematuria is intermittent and may not be detected until adulthood. Episodic gross hematuria, often in association with upper respiratory tract infections, which is typical for IgAN, is not unusual. TBMN was originally known to have a benign clinical course associated with family history. Overt proteinuria and hypertension are unusual in TBMN. Other glomerular disorders, such as IgAN and focal or global glomerulosclerosis, may occur concurrently with TBMN, altering the usual natural clinical course and histopathology of the condition [6]. Voskarides et al. reported that in cases of combined focal segmental glomerulosclerosis on biopsy, the prognosis was not good in a significant proportion of patients [9]. TBMN mainly manifests as an inherited disorder with autosomal dominant transmission affecting approximately one-half of successive generations. Approximately two-thirds of patients with TBMN have at least one other relative with hematuria. The remaining one-third of patients may have de novo mutations or the nonpenetrance in other members of the family. About half of TBMN is caused by the mutation of COL4A3/COL4A4 genes …