Effect of angiotensin converting enzyme gene I/D polymorphism in South Indian children with nephrotic syndrome.

Nephrotic syndrome is one of the most common childhood kidney diseases. It is mostly found in the age group of 2 to 8 years. Around 10%-15% of nephrotic syndrome cases are non-responders of steroid treatment (SRNS). Angiotensin converting enzyme (ACE) (I/D) gene association studies are important for detecting kidney disease and herein we assessed the association of ACE (I/D) polymorphism with nephrotic syndrome in South Indian children. We recruited 260 nephrotic syndrome (162 boys and 98 girls) and 218 (140 boys and 78 girls) control subjects. ACE I/D polymorphism was analyzed by PCR using genotype allele specific primers. In ACE (I/D), we did not find significant association for the ungrouped data of nephrotic syndrome children and the control subjects. Kidney biopsies were done in 86 nephrotic syndrome cases (minimal change disease, n=51; focal segmental glomerulosclerosis, n=27; diffuse mesangial proliferation, n=8). We segregated them into the minimal change disease / focal segmental glomerulosclerosis groups and observed that the ACE'D' allele was identified with borderline significance in cases of focal segmental glomerulosclerosis and the 'I' allele was assessed as having very weak association in cases of minimal change disease. 'II' genotype was weakly associated with minimal change disease. Gender specific analysis revealed weak association of 'ID' genotype with female nephrotic syndrome in females. Dominant expression of DD genotype was observed in males with nephrotic syndrome. Our finding indicated that ACE (I/D) has moderate association with focal segmental glomerulosclerosis. However, due to the limited number of biopsy proven focal segmental glomerulosclerosis subjects enrolled, further studies are required to confirm these results.

Susceptible and Protective Associations of HLA Alleles and Haplotypes with Cervical Cancer in South India.

BACKGROUND: Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. OBJECTIVES: To study the predispositions of HLA alleles/haplotypes with cervical cancer. MATERIALS AND METHODS: Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. RESULTS: The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; < 3.5.10-4), DRB1*14-DQB1*0501 (OR=6.51; <0.039) and A*11-B*07 (OR=3.95; <0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; <0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions ß9 and ß37 and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer. CONCLUSIONS: Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India.

Hsp70 is an independent stress marker among frequent users of mobile phones.

The aim of this study was to measure the serum concentrations of heat shock protein (HSP) 70 and C-reactive protein (CRP) and the expression levels of the hsp70 gene among frequent users of mobile phones (FUMPs). We enrolled 120 employees of information technology (IT)/IT enabled service companies (FUMPs; IT professionals) and 102 infrequent users of mobile phones (IFUMPs; people from non-IT professions) as controls. The serum concentrations of HSP70 and CRP were measured by enzyme-linked immunosorbant assay and hsp70 gene expression by reverse transcription polymerase chain reaction. Significantly higher concentrations of serum HSP70 (P < 0.00012) and CRP (P < 0.04) were observed among FUMPs than IFUMPs. A higher level of hsp70 gene expression (fold induction) was observed among FUMPs than IFUMPs (P < 7.06 × 10-13). In contrast to the duration of exposure-dependent increase of serum concentration of CRP, the serum HSP70 concentration was found to be independent of the duration of exposure to mobile phones. Thus, the study convincingly demonstrated the role of serum HSP and CRP as systemic inflammatory biomarkers for mobile phone-induced radiation.