HLA-G exon 8 polymorphism in type 1 diabetes among north Indians

Manish Mourya, Nikhil Tandon, Prashant Sood, A Saxena, Poonam Coshic, NK Mehra, Uma Kanga

Research output: Contribution to journalAbstract

Abstract

Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic islet beta cells. Genetic susceptibility to T1D due to human leukocyte antigens (HLAs) on chromosome 6p21 region, particularly,HLA-DRB1*03 and*04 has been reported worldwide, however, not all DR3 or DR4 haplotypes predispose equally to the disease. HLA-G, a non-classical class Imolecule is involved in induction and maintenance of tolerance and therefore implicated in the pathogenesis of various autoimmune diseases, infections, cancers and transplantation. A 14-bp insertion (+14 bp) in the 3′-untranslated region of the HLA-Gexon 8 leads to an unstable mRNA and a lower soluble HLA-G(sHLA-G) levels. Differential ability to counteract inflammation between 14-bp genotypes and a potential role of sHLA-G as immunomodulatory factor has been suggested. The role of HLA-G in T1D is not well known. Induction of HLA-G expression on dendritic cells from diabetic subjects mediated the inhibition of autologous T cell activation, indicating the role in diabetic pathogenesis. A report on conditional analysis among∼2400 T1D affected families revealed novel association around the HLA-Glocus. The present study was aimed at evaluating the possible association of 14-bp INDEL polymorphism with T1D in North Indian population. Study subjects included 78 T1D cases from our centre and ethnically matched 70 healthy controls (HCs).The+14-bp allele was observed more frequently in T1D cohort compared with healthy controls (53% vs 47%). Genotype analysis revealed presence of+14/+14 bp in 31% of T1D cases and in only 20.5% of HCs. Segregation of study cohort on basis of the presence or absence of the T1D susceptibility HLA allele(DR3) revealed interesting results. Among the DR3+ve group,the low sHLA secretary+/+14-bp genotype was more common in patients than controls (28%vs9%). On the other hand, high secretary genotype,−/−14 bp was more frequent in the HCs(55%vs28%) than patients. Similar analysis of DR3-ve cohort revealed that a higher number of T1D cases carried the low sec-retary+/+genotype (43%vs22%,P=0.04). These findings suggest that in DR3+ve controls, presence of high secretary−/−14-bp genotype inhibited the auto reactive T cells and was probably beneficial, whereas in DR3-ve T1D cohort, this inhibition may not have been possible due to presence of low secretary 14-bp genotype. Estimation of sHLA-G levels in our cohort is currently in process and its correlation with above findings may reveal better information. The preliminary findings suggest that 14-bpINDEL polymorphism may influence the diabetes pathogenesis in our study cohort
Original languageEnglish
Pages (from-to)102
Number of pages1
JournalTissue Antigens
Volume80
Issue number1
Early online date1 Jun 2012
DOIs
Publication statusPublished - Jul 2012

Fingerprint

Medical problems
HLA Antigens
Polymorphism
Type 1 Diabetes Mellitus
Exons
Genotype
HLA-G Antigens
T-cells
Islets of Langerhans
Autoimmune Diseases
Cohort Studies
Alleles
Association reactions
T-Lymphocytes
Aptitude
Insulin-Secreting Cells
3' Untranslated Regions
Genetic Predisposition to Disease
Chromosomes
Dendritic Cells

Keywords

  • HLA ANTIGENS

Cite this

Mourya, M., Tandon, N., Sood, P., Saxena, A., Coshic, P., Mehra, NK., & Kanga, U. (2012). HLA-G exon 8 polymorphism in type 1 diabetes among north Indians. Tissue Antigens, 80(1), 102. https://doi.org/10.1111/j.1399-0039.2012.01899.x

HLA-G exon 8 polymorphism in type 1 diabetes among north Indians. / Mourya, Manish; Tandon, Nikhil; Sood, Prashant; Saxena, A; Coshic, Poonam; Mehra, NK; Kanga, Uma.

In: Tissue Antigens, Vol. 80, No. 1, 07.2012, p. 102.

Research output: Contribution to journalAbstract

Mourya, M, Tandon, N, Sood, P, Saxena, A, Coshic, P, Mehra, NK & Kanga, U 2012, 'HLA-G exon 8 polymorphism in type 1 diabetes among north Indians', Tissue Antigens, vol. 80, no. 1, pp. 102. https://doi.org/10.1111/j.1399-0039.2012.01899.x
Mourya M, Tandon N, Sood P, Saxena A, Coshic P, Mehra NK et al. HLA-G exon 8 polymorphism in type 1 diabetes among north Indians. Tissue Antigens. 2012 Jul;80(1):102. https://doi.org/10.1111/j.1399-0039.2012.01899.x
Mourya, Manish ; Tandon, Nikhil ; Sood, Prashant ; Saxena, A ; Coshic, Poonam ; Mehra, NK ; Kanga, Uma. / HLA-G exon 8 polymorphism in type 1 diabetes among north Indians. In: Tissue Antigens. 2012 ; Vol. 80, No. 1. pp. 102.
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T1 - HLA-G exon 8 polymorphism in type 1 diabetes among north Indians

AU - Mourya, Manish

AU - Tandon, Nikhil

AU - Sood, Prashant

AU - Saxena, A

AU - Coshic, Poonam

AU - Mehra, NK

AU - Kanga, Uma

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N2 - Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic islet beta cells. Genetic susceptibility to T1D due to human leukocyte antigens (HLAs) on chromosome 6p21 region, particularly,HLA-DRB1*03 and*04 has been reported worldwide, however, not all DR3 or DR4 haplotypes predispose equally to the disease. HLA-G, a non-classical class Imolecule is involved in induction and maintenance of tolerance and therefore implicated in the pathogenesis of various autoimmune diseases, infections, cancers and transplantation. A 14-bp insertion (+14 bp) in the 3′-untranslated region of the HLA-Gexon 8 leads to an unstable mRNA and a lower soluble HLA-G(sHLA-G) levels. Differential ability to counteract inflammation between 14-bp genotypes and a potential role of sHLA-G as immunomodulatory factor has been suggested. The role of HLA-G in T1D is not well known. Induction of HLA-G expression on dendritic cells from diabetic subjects mediated the inhibition of autologous T cell activation, indicating the role in diabetic pathogenesis. A report on conditional analysis among∼2400 T1D affected families revealed novel association around the HLA-Glocus. The present study was aimed at evaluating the possible association of 14-bp INDEL polymorphism with T1D in North Indian population. Study subjects included 78 T1D cases from our centre and ethnically matched 70 healthy controls (HCs).The+14-bp allele was observed more frequently in T1D cohort compared with healthy controls (53% vs 47%). Genotype analysis revealed presence of+14/+14 bp in 31% of T1D cases and in only 20.5% of HCs. Segregation of study cohort on basis of the presence or absence of the T1D susceptibility HLA allele(DR3) revealed interesting results. Among the DR3+ve group,the low sHLA secretary+/+14-bp genotype was more common in patients than controls (28%vs9%). On the other hand, high secretary genotype,−/−14 bp was more frequent in the HCs(55%vs28%) than patients. Similar analysis of DR3-ve cohort revealed that a higher number of T1D cases carried the low sec-retary+/+genotype (43%vs22%,P=0.04). These findings suggest that in DR3+ve controls, presence of high secretary−/−14-bp genotype inhibited the auto reactive T cells and was probably beneficial, whereas in DR3-ve T1D cohort, this inhibition may not have been possible due to presence of low secretary 14-bp genotype. Estimation of sHLA-G levels in our cohort is currently in process and its correlation with above findings may reveal better information. The preliminary findings suggest that 14-bpINDEL polymorphism may influence the diabetes pathogenesis in our study cohort

AB - Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic islet beta cells. Genetic susceptibility to T1D due to human leukocyte antigens (HLAs) on chromosome 6p21 region, particularly,HLA-DRB1*03 and*04 has been reported worldwide, however, not all DR3 or DR4 haplotypes predispose equally to the disease. HLA-G, a non-classical class Imolecule is involved in induction and maintenance of tolerance and therefore implicated in the pathogenesis of various autoimmune diseases, infections, cancers and transplantation. A 14-bp insertion (+14 bp) in the 3′-untranslated region of the HLA-Gexon 8 leads to an unstable mRNA and a lower soluble HLA-G(sHLA-G) levels. Differential ability to counteract inflammation between 14-bp genotypes and a potential role of sHLA-G as immunomodulatory factor has been suggested. The role of HLA-G in T1D is not well known. Induction of HLA-G expression on dendritic cells from diabetic subjects mediated the inhibition of autologous T cell activation, indicating the role in diabetic pathogenesis. A report on conditional analysis among∼2400 T1D affected families revealed novel association around the HLA-Glocus. The present study was aimed at evaluating the possible association of 14-bp INDEL polymorphism with T1D in North Indian population. Study subjects included 78 T1D cases from our centre and ethnically matched 70 healthy controls (HCs).The+14-bp allele was observed more frequently in T1D cohort compared with healthy controls (53% vs 47%). Genotype analysis revealed presence of+14/+14 bp in 31% of T1D cases and in only 20.5% of HCs. Segregation of study cohort on basis of the presence or absence of the T1D susceptibility HLA allele(DR3) revealed interesting results. Among the DR3+ve group,the low sHLA secretary+/+14-bp genotype was more common in patients than controls (28%vs9%). On the other hand, high secretary genotype,−/−14 bp was more frequent in the HCs(55%vs28%) than patients. Similar analysis of DR3-ve cohort revealed that a higher number of T1D cases carried the low sec-retary+/+genotype (43%vs22%,P=0.04). These findings suggest that in DR3+ve controls, presence of high secretary−/−14-bp genotype inhibited the auto reactive T cells and was probably beneficial, whereas in DR3-ve T1D cohort, this inhibition may not have been possible due to presence of low secretary 14-bp genotype. Estimation of sHLA-G levels in our cohort is currently in process and its correlation with above findings may reveal better information. The preliminary findings suggest that 14-bpINDEL polymorphism may influence the diabetes pathogenesis in our study cohort

KW - HLA ANTIGENS

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DO - 10.1111/j.1399-0039.2012.01899.x

M3 - Abstract

VL - 80

SP - 102

JO - Tissue Antigens

JF - Tissue Antigens

SN - 0001-2815

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ER -