Correlation between a gene polymorphism of tumor necrosis factor-alpha (G/A) and end-stage renal disease: a pilot study from north India.
BACKGROUND
Patients with chronic kidney disease manifest an inflammatory state in comparison to healthy individuals. Tumor necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory cytokine involved in initiation and progression of renal injury. We examined the 2-promoter region polymorphism of TNF-alpha gene G to A at -308 and at +488 sites in end-stage renal disease (ESRD) subjects.


METHODS
The TNF-alpha -308 G/A and +488 G/A polymorphisms were genotyped in 231 patients aged 36.5+/-10, and in 180 matched controls (34.96+/-11.3) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS-PCR) method, respectively.


RESULTS
The genotypic distribution of TNF-alpha -308 and +488 were significantly different between patients and controls (P<0.001 and P<0.006), respectively. The AA genotype was more frequent in ESRD patients than controls for both the sites (42% vs. 2.8% and 17.3% vs. 2.2%), respectively. The allelic frequency of TNF-alpha A was also higher in cases than in controls for both the sites (P<0.001; OR=2.96; 95% CI=2.228-3.945 and P<0.013; OR=1.422; 95% CI=1.078-1.876). Significant difference was observed for haplotype frequency distribution between ESRD patients and controls and 'A-G#' haplotype showed >9-fold higher risk (OR=9.886, 95% CI=4.408-22.172). The two polymorphisms were in linkage disequilibrium in the control group (D'=0.8047, P<0.001).


CONCLUSIONS
Both the variants of TNF-alpha (-308 and +488) polymorphism had significant association and may thus be a strong predisposing risk factor for ESRD in a cohort of north Indian population. Further, individuals with haplotypes A-G# may be at higher risk for ESRD.
Sanjay Gandhi Post Graduate Institute of Medical Sciences Lucknow, Uttar Pradesh, India.
Parmeet Kaur
PK
Manchanda
Anant
A
Kumar
Anupma
A
Kaul
Rama Devi
RD
Mittal
D000241:Adenosine / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D005838:Genotype; D005921:Glomerulonephritis / Q000235:genetics; D006151:Guanosine / Q000235:genetics*; D006801:Humans; D007194:India; D007676:Kidney Failure, Chronic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009401:Nephrosis / Q000209:etiology / Q000235:genetics; D010865:Pilot Projects; D011110:Polymorphism, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D006151:Guanosine; D000241:Adenosine