Associations of CTLA4 +49 A/G Dimorphism and HLA-DRB1*/DQB1* Alleles With Type 1 Diabetes from South India.

The aim of present study was to elucidate the association of CTLA4 +49 A/G and HLA-DRB1*/DQB1* gene polymorphism in south Indian T1DM patients. The patients and controls (n = 196 each) were enrolled for CTLA4 and HLA-DRB1*/DQB1* genotyping by RFLP/PCR-SSP methods. The increased frequencies of CTLA4 'AG' (OR = 1.99; p = 0.001), 'GG' (OR = 3.94; p = 0.001) genotypes, and 'G' allele (OR = 2.42; p = 9.26 × 10-8) were observed in patients. Reduced frequencies of 'AA' (OR = 0.35; p = 7.19 × 10-7) and 'A' (OR = 0.41; p = 9.26 × 10-8) in patients revealed protective association. Among HLA-DRB1*/DQB1* alleles, DRB1*04 (OR = 3.29; p = 1.0 × 10-5), DRB1*03 (OR = 2.81; p = 1.9 × 10-6), DQB1*02:01 (OR = 2.93; p = 1.65 × 10-5), DQB1*02:02 (OR = 3.38; p = 0.0003), and DQB1*03:02 (OR = 7.72; p = 0.0003) were in susceptible association. Decreased frequencies of alleles, DRB1*15 (OR = 0.32; p = 2.55 × 10-7), DRB1*10 (OR = 0.45; p = 0.002), DQB1*06:01 (OR = 0.43; p = 0.0001), and DQB1*05:02 (OR = 0.28; p = 2.1 × 10-4) in patients were suggested protective association. The combination of DRB1*03+AG (OR = 5.21; p = 1.4 × 10-6), DRB1*04+AG (OR = 2.14; p = 0.053), DRB1*04+GG (OR = 5.21; p = 0.036), DQB1*02:01+AG (OR = 4.44; p = 3.6 × 10-5), DQB1*02:02+AG (OR = 20.9; p = 9.5 × 10-4), and DQB1*02:02+GG (OR = 4.06; p = 0.036) revealed susceptible association. However, the combination of DRB1*10+AA (OR = 0.35; p = 0.003), DRB1*15+AA (OR = 0.22; p = 5.3 × 10-7), DQB1*05:01+AA (OR = 0.45; p = 0.007), DQB1*05:02+AA (OR = 0.17; p = 1.7 × 10-4), DQB1*06:01+AA (OR = 0.40; p = 0.002), and DQB1*06:02+AG (OR = 0.34; p = 0.001) showed decreased frequency in patients, suggesting protective association. In conclusion, CTLA4/HLA-DR/DQ genotypic combinations revealed strong susceptible/protective association toward T1DM in south India. A female preponderance in disease associations was also documented.

Interaction of HLA-DRB1* alleles and CTLA4 (+49 AG) gene polymorphism in Autoimmune Thyroid Disease.

Autoimmune Thyroid Diseases (AITDs), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), arise by the complex interaction of genes and environmental factors. The aim of present study was to study the susceptible associations of HLA-DRB1* alleles and CTLA4 +49 AG polymorphism in AITD in south India. AITD patients (n=235; HT=180; GD=55) and age/sex matched healthy controls (n, 235) were enrolled to type HLA-DRB1* alleles and 'CTLA4 +49 AG' by PCR-SSP and PCR-RFLP methods respectively. Analysis revealed CTLA4 +49 'GG' genotype was increased significantly in patients (PL: p=8.7×10-8; HT: p=9.3×10-6; GD: p=0.006). Decreased frequencies of 'AA' genotype was observed in patients (PL: p=9.4×10-6; HT: p=0.008; GD: p=9.0×10-6). Increased frequencies were observed for HLA alleles DRB1*12 (PL: p=1.42×10-10; HT: p=5.75×10-8; GD: p=0.002) and DRB1*11 (PL: p=0.0025; HT: p=0.013) in patients. Decreased frequencies for alleles DRB1*10 (PL: p=0.00002; HT: p=0.018; GD: p=1.63×10-5) and DRB1*03 (PL: p=0.003; HT: p=0.003) were observed, suggesting a protective association. Combinatorial/Synergistic analysis have revealed an increased frequencies for 'DRB1*11+AG' (PL: p=0.022), 'DRB1*12+AG' (PL: p=6.1×10-5; HT: p=0.0001), 'DRB1*04+GG' (PL: p=0.003; HT: p=0.008), 'DRB1*07+GG' (PL: p=0.009; HT: p=0.014) and 'DRB1*12+GG' (PL: p=0.005; HT: p=0.005) in patients. However, the combinations such as 'DRB1*10+AA' (PL: p=1.8×10-6; HT: p=0.003) and 'DRB1*15+AA' (PL: p=0.006; GD: p=0.011) were decreased in patients showing a protective association. The 'GG/G' of CTLA4 +49AG SNP, HLA-DRB1*11/-DRB1*12 (DR5) alleles and the combinations of DRB1*11/DRB1*12 alleles with AG/GG genotype and DRB1*04/07/12 alleles with GG genotype may act as synergistic manner to confer the strong susceptibility to AITD in south India.

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.