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Stroke has emerged as the second commonest cause of mortality worldwide and is a major public health problem. For the first time, we present here the association of human leucocyte antigen (HLA)-DRB1*/DQB1* alleles and haplotypes with ischaemic stroke in South Indian patients. Ischaemic stroke (IS) cases and controls were genotyped for HLA-DRB1*/DQB1* alleles by polymerase chain reaction sequence-specific primers (PCR-SSP) method. The frequencies of HLA class II alleles such as DRB1*04, DRB1*07, DRB1*11, DRB1*12, DRB1*13, DQB1*02 and DQB1*07 were high in IS patients than in the age- and gender-matched controls, suggesting that the individuals with these alleles are susceptible to ischaemic stroke in South India. The frequencies of alleles such as DRB1*03, DRB1*10, DRB1*14, DQB1*04 and DQB1*05 were less in IS cases than in the controls, suggesting a protective association. Haplotypes DRB1*04-DQB1*0301, DRB1*07-DQB1*02, DRB1*07-DQB1*0301, DRB1*11-DQB1*0301 and DRB1*13-DQB1*06 were found to be high in IS patients conferring susceptibility. The frequency of haplotype DRB1*10-DQB1*05 was high in controls conferring protection. IS-LVD and gender-stratified analysis too confirmed these susceptible and protective associations. Thus, HLA-DRB1*/DQB1* alleles and haplotypes strongly predispose South Indian population to ischaemic stroke. Further studies in different populations with large sample size or the meta-analysis are needed to explain the exact mechanism of associations of HLA gene(s) with IS.

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.

The HLA-DQB1* region exhibits complex associations with autoimmune thyroid disease (AITD). AITD patients (Hashimoto’s thyroiditis, HT = 180; Graves’ disease, GD = 55) and age/sex matched controls (n = 235) were genotyped for DQB1* alleles by PCR-SSP. Alleles DQB1*02:02, *06:03, *06:09, *03:02, and *03:03 showed an increased risk and *02:01, *05:02, and *06:02 showed a protection toward AITD. Multiple sequence alignment was used to find out the amino acid variations within the peptide-binding pockets of susceptible and/or protective DQB1* alleles. We observed susceptible associations for amino acids ‘Glu86(P

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.

Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations.To study the predispositions of HLA alleles/haplotypes with cervical cancer.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.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 β9 and β37 and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer.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.