Lymphotoxin-alpah gene polymorphism in patients with glomerulonephritis

Lee, Eun Young; Hong, Sae Yong; Choi, Jong Soon; Yang, Dong Ho; Cho, Jong Tae; Yoon, Sung Chul

Abstract

BACKGROUND: Lymphotoxin (LT)-alpha is a cytokine that has been involved in the inflammatory response, the pathogenesis of autoimmune disease, and the development and progression of renal injury in various glomerulonephritis. Glomerulonephritis is an important cause of end-stage renal disease requiring renal replacement therapy. A great body of evidence suggests that immunologic mechanisms and genetic factor such as gene polymorphism play an important role in the renal injury of glomerulonephritis. However, the role of LT-alpha gene polymorphism in primary glomerulonephritis is not clear yet. The purpose of this study is to examine whether there are the associations between LT-alpha gene polymorphisms and the development and progression of various primary glomerulonephritis.
METHODS
A cross-sectional study of LT-alpha gene polymorphism by polymerase chain reaction with restriction fragment length polymorphism was performed on 190 patients with primary glomerulonephritis confirmed by renal biopsy and 249 controls. The gene polymorphism in the first intron of LT-alpha gene was detected by digestion with Nco1 restriction enzyme and subsequent electrophoresis. The clinical parameters at renal biopsy and the latest follow-up were collected.
RESULTS
LTA1/LTA1 : LTA1/LTA2 : LTA2/LTA2 genotype distribution of the LT-alpha gene in the study population was 0.12 : 0.54 : 0.34, and the LTA1 : LTA2 allele frequency was 0.39 : 0.61. Thirty-one minimal change disease, 33 focal segmental glomerulosclerosis, 18 membranous glomerulonephritis, 16 membranoproliferative glomerulonephritis, and 92 InA nephropathy were included in this study. The distribution of LTA1/LTA1 : LTA1/LTA2 : LTA2/LTA2 was significantly different in the membranous glomerulonephritis (0.33 : 0.39 : 0.28, p<0.001) with control groups. But, there were no significant differences between the distributions of LT-alpha genotype in the patients with other glomerulonephritis groups. There were no significant differences in the age, systolic and diastolic blood pressure, serum creatinine, cholesterol, and proteinuria at renal biopsy among the three genotypes. There was no significant difference in the incidence of patients who started dialysis treatment or whose serum creatinine was double or more during the follow-up duration which was more than four years among the three genotypes.
CONCLUSION
These data suggested that polymorphism in the LT-alpha gene may be associated with the development of primary membranous glomerulonephritis, however, these are not directly associated with the progression of renal injury in various glomerulonephritis.