Major histocompatibility complex class I chain related gene‐A microsatellite polymorphism shows secondary association with type 1 diabetes and celiac disease in North Indians

Kumar, Neeraj; Sharma, Gaurav; Kaur, Gurvinder; Tandon, Nikhil; Bhatnagar, Shinjini; Mehra, N. K.

doi:10.1111/j.1399-0039.2012.01931.x

Cited by 15 publications

(10 citation statements)

References 45 publications

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“…The difference in the prevalence of CD across geographical locations was found to be due to difference in distribution of the HLA genotypes and its complex interaction with the environment and host immunological factors19. The association of T1DM and CD in north Indian population may be attributed to microsatellite polymorphism in major histocompatibility complex class I chain20. A multicentre study from Italy has demonstrated a positive association between young age at diabetes onset, female gender and the development of CD21.…”

Section: Discussionmentioning

confidence: 99%

Coexistence of celiac disease & type 1 diabetes mellitus in children

Singh¹,

Seth²,

Kumar³

et al. 2017

Indian J Med Res

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Background & objectives:Type 1 diabetes mellitus (T1DM) and celiac disease (CD) tend to co-exist due to similar underlying genetic predisposition. Failure to recognize CD in patients with T1DM predisposes them to complications. The present study was aimed to assess children with T1DM for the presence of CD.Methods:This was a retrospective analysis of the records of children with T1DM attending paediatric endocrinology clinic at a tertiary care hospital in north India from January 2006 to May 2014. All children were screened for CD at the time of diagnosis of T1DM using IgA anti-tissue transglutaminase (anti-tTG) levels in serum. Seropositive children were subjected to upper gastrointestinal endoscopy and duodenal biopsy for histopathological confirmation. The children also underwent thyroid function testing (TFT); those with deranged TFT were evaluated for thyroid-specific antibodies.Results:Positive serology for CD was present in 43 of 126 children with T1DM whose records were reviewed [34.1%; 95% confidence interval (CI): 25.9-43.1]. Confirmed CD was diagnosed in 17 (13.5%; CI: 8.1-20.7) of the children screened and 17 of 40 (42.5%; CI: 27.1-59.1) seropositive participants. Four out of 17 children with coexisting CD and T1DM also had autoimmune thyroiditis with overt hypothyroidism. The children with confirmed CD were more likely to have short stature [odds ratios (OR)-3.16; 95% CI: 1.09-9.20, P<0.05] and hypothyroidism (OR-6.4; 95% CI: 1.52-26.90, P<0.05).Interpretation & conclusions:Our study showed a higher proportion of CD in children with T1DM as compared to that reported in general population. Regular screening of children with T1DM for CD is needed to improve metabolic control and prevent long-term complications.

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Section: Discussionmentioning

confidence: 99%

Coexistence of celiac disease & type 1 diabetes mellitus in children

Singh¹,

Seth²,

Kumar³

et al. 2017

Indian J Med Res

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“…The exon encodes membrane-binding domain of the protein [90]. The microsatellite alleles are associated with Addison's disease [90], type 1 diabetes mellitus [91,92,93]. Some alleles are protective against juvenile idiopathic arthritis [94].…”

Section: Dna Secondary Structurementioning

confidence: 99%

Structural and functional significance of microsatellites

2016

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Here we review literature data on impact of microsatellite repeats on DNA and chromatin structure and the results of studies on association between the length of microsatellite repeats and predisposition to pathologies. The DNA secondary structure is modified in microsatellite sites, the repeats favour formation of Z-DNA, hairpins, triplexes and quadruplexes. The chromatin structure and chromatin loop organization are also modified in microsatellite sites. The data of association studies are classified according to the localization of the microsatellite: in the gene promoter, in exon 1 part coding the signal sequence, in the gene introns, coding area s and 3'-UTRs.

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“…It was found that DR3 positive MICA5.1 positive and DR3+MICA5.1 negative individuals have similar relative risk suggesting that MICA5.1 has no independent association with T1DM. [ 3 ]…”

Section: O Ther G Enesmentioning

confidence: 99%

Understanding type 1 diabetes through genetics: Advances and prospects

Tandon

2015

Indian J Endocr Metab

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The largest contribution of type 1 diabetes mellitus (T1DM) from a single locus comes from several genes located in the major histocompatibility complex on chromosome 6p21. Because DQB1 is the best single genetic marker for T1DM, it is the gene most often used to identify individuals with a high risk of developing disease. As per the data collected from the All India Institute of Medical Sciences, among the human leukocyte antigen (HLA)-DRB1 genes, HLA-DR3 showed strongest association with the disease; however, unlike Caucasians and other populations, DR4 was not significantly increased in these patients. HLA-DR10, 11, 13, and 15 showed a negative association with the disease as they were reduced in these patients. In India, the relative risk of developing T1DM is higher with the DR3-DQ2 haplotypes as compared to DR4-DQ8 haplotypes. Studies have shown that in North India, the relative risk for T1DM is comparatively higher (>30) with the DQ2/DQ8 genotype, but is relatively lower (approximately 18) for the DQ2/DQ2 genotype. In addition, the three sets of HLA-B-DR3 haplotypes, mainly B58-DR3, B50-DR3, and B8-DR3 have shown to have modulated susceptibility for T1DM in India and worldwide. New interventions that will be tested in the future will be conducted through T1DM TrialNet, a collaborative network of clinical centers and experts in diabetes and immunology. These studies will identify unaffected first-degree relatives with beta cell autoantibodies who will be eligible for new interventions.

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Major histocompatibility complex class I chain related gene‐A microsatellite polymorphism shows secondary association with type 1 diabetes and celiac disease in North Indians

Cited by 15 publications

References 45 publications

Coexistence of celiac disease & type 1 diabetes mellitus in children

Coexistence of celiac disease & type 1 diabetes mellitus in children

Structural and functional significance of microsatellites

Understanding type 1 diabetes through genetics: Advances and prospects

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