HLA class II SNP interactions and the association with type 1 diabetes mellitus in Bengali speaking patients of Eastern India

Abstract

BackgroundSeveral studies have demonstrated a fundamental role for the HLA in the susceptibility of, or protection to, type 1 diabetes mellitus (T1DM). However, this has not been adequately studied in Asian Indian populations. To assess the frequency of HLA class II (DPA1, DPB1, DQA1, DQB1 and DRB1) associated to susceptibility or protection toT1DM in a Bengali population of India with diabetes.ResultsSingle nucleotide polymorphism study. The HLA genotyping was performed by a polymerase chain reaction followed by their HLA-DP, DQ, and DRB1 genotypes and haplotypes by sequencing method. The results are studied by Plink software. The χ2 tests were used for the inferential statistics. To our knowledge, this study is the first of a kind which has attempted to check the HLA association with T1DM by SNPs analysis. The study recruited 151 patients with T1DM and same number of ethno-linguistic, sex matched non-diabetic controls. The present study found a significant SNP rs7990 of HLA-DQA1 (p = 0.009) negative correlation, again indicating that risk from HLA is considerably more with T1DM.ConclusionsThis study demonstrates that the HLA class-II alleles play a major role in genetic basis of T1DM.

Association of insulin gene VNTR INS -23/Hph1 A>T (rs689) polymorphism with type 1 diabetes mellitus in Egyptian children

“…Other reports, however, deny any impact of INSrs689 polymorphism on risk susceptibility to TIDM [16][17][18][19][20]. The study of Benedek et al [14] that documented the association of T allele with ITD in three Jewish populations failed to prove that association in the Israeli Arabs which highlights the effect of ethnicity.…”

“…Apart from this mechanistic theory, risk susceptibility associated with gene polymorphisms is largely affected by ethnic variations including the relative genotype frequency in different populations which varies from one community to another [12,13,16,33,34,37].…”

“…In some reports, the A allele is claimed to be associated with risk of developing diabetes and the T allele is claimed to be protective [8][9][10][11][12]. Other reports indicate that T allele is the one associated with risk susceptibility [13][14][15] while others deny an impact of either on risk susceptibility to TIDM [16][17][18][19][20].…”

The Relationship between insulin variable number of tandem repeats (INS-VNTR) -23 A/T and cytotoxic T-lymphocyte associated protein-4 (CTLA-4) +49 A/G polymorphisms with islet autoantibodies in persons with diabetes

“…These are INS-VNTR and CTLA-4. Together, these two genes confer an inheritable disease risk no larger than 15% (19,20) (25). Also, Cejkova P et al showed that the genotype and allele frequencies of -23 HphI did not differ between T1DM, LADA and T2DM groups and group of healthy subjects in population of the Czech Republic (26).…”

Human Genes Encoding Transcription Factors and Chromatin-Modifying Proteins Have Low Levels of Promoter Polymorphism: A Study of 1000 Genomes Project Data

“…For example, it was estimated that the G → T substitution (rs1271572) in the ERβ promoter prevented transcription factor Yin Yang 1 (YY1) binding and reduced its transcription activity. The TT genotype for rs1271572 was associated with elevated risk for breast cancer in Chinese women and with unfavorable prognosis in Chinese breast cancer patients [ 18 ].…”