PMID- 22723329 OWN - NLM STAT- MEDLINE DCOM- 20121126 LR - 20220408 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 97 IP - 9 DP - 2012 Sep TI - Presence of strong association of the major histocompatibility complex (MHC) class I allele HLA-A*26:01 with idiopathic hypoparathyroidism. PG - E1820-4 LID - 10.1210/jc.2012-1328 [doi] AB - CONTEXT: The pathogenesis of isolated hypoparathyroidism, also referred to as idiopathic hypoparathyroidism (IH), is not clear. There is a paucity of information related to the immunogenetic basis of the disease due to its rarity. A recurrent theme of several autoimmune disorders is aberrant antigen presentation. OBJECTIVE: We investigated for the association of alleles of the human leukocyte antigen (HLA) class I and II loci with IH. PATIENTS AND CONTROLS: A total of 134 patients with IH and 902 healthy controls from the same ethnic background participated in the study. RESULTS: There was a significant increase of HLA class I alleles HLA-A*26:01 [P < 1.71 x 10(-34); odds ratio (OR) = 9.29; 95% confidence interval (CI) = 6.08-14.16] and HLA-B*08:01 (P < 8.19 x 10(-6); OR = 2.59; 95% CI = 1.63-4.04) in patients with IH compared to healthy controls. However, the association of A*26:01 was primary because B*08:01 was in linkage disequilibrium with A*26:01. Although the major histocompatibility complex (MHC) is very polymorphic, several alleles of HLA loci share key residues at anchor positions in the peptide binding pockets such that similar peptides may be presented by different MHC molecules encoded by the same locus. These allelic forms with similar anchoring amino acids have been clustered in supertypes. An analysis of HLA-A locus supertypes A01, A02, A03, and A04 revealed that supertype A01 was significantly increased (P < 9.18 x 10(-9); OR = 2.95) in IH compared to controls. However, this increase in the supertype A01 was contributed by A*26:01 because 68.7% of the A01 samples had A*26:01. Other alleles of the supertype did not show any significant differences. CONCLUSION: The strong association of HLA-A*26:01 suggests an important role of MHC class I-mediated presentation of autoantigenic peptides to CD8(+) cytotoxic T cells in the pathogenesis of IH. These data provide evidence for the autoimmune etiology of IH akin to other autoimmune disorders like type 1 diabetes and rheumatoid arthritis. FAU - Goswami, Ravinder AU - Goswami R AD - Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi 110029, India. FAU - Singh, Archana AU - Singh A FAU - Gupta, Nandita AU - Gupta N CN - Indian Genome Variation Consortium FAU - Rani, Rajni AU - Rani R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120620 PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Amino Acids) RN - 0 (HLA-A Antigens) RN - 0 (HLA-A*26:01 antigen) RN - 0 (HLA-B Antigens) RN - 0 (HLA-DRB1 Chains) RN - 0 (Peptides) SB - IM MH - Adult MH - Alleles MH - Amino Acids/chemistry MH - Female MH - Gene Frequency MH - Genes, MHC Class I/*genetics MH - Genetic Association Studies MH - HLA-A Antigens/*genetics MH - HLA-B Antigens/genetics MH - HLA-DRB1 Chains/genetics MH - Haplotypes MH - Humans MH - Hypoparathyroidism/epidemiology/*genetics MH - India/epidemiology MH - Male MH - Middle Aged MH - Peptides/chemistry FIR - Brahmachari, Samir K IR - Brahmachari SK FIR - Majumder, Partha P IR - Majumder PP FIR - Mukerji, Mitali IR - Mukerji M FIR - Habib, Saman IR - Habib S FIR - Dash, Debasis IR - Dash D FIR - Ray, Kunal IR - Ray K FIR - Bahl, Samira IR - Bahl S FIR - Singh, Lalji IR - Singh L FIR - Sharma, Abhay IR - Sharma A FIR - Roychoudhury, Susanta IR - Roychoudhury S FIR - Chandak, G R IR - Chandak G FIR - Thangaraj, K IR - Thangaraj K FIR - Parmar, D IR - Parmar D FIR - Sengupta, Shantanu IR - Sengupta S FIR - Bharadwaj, Dwaipayan IR - Bharadwaj D FIR - Rath, Srikanta K IR - Rath SK FIR - Singh, Jagmohan IR - Singh J FIR - Jha, Ganga Nath IR - Jha GN FIR - Virdi, Komal IR - Virdi K FIR - Rao, V R IR - Rao V FIR - Sinha, Swapnil IR - Sinha S FIR - Singh, Ashok IR - Singh A FIR - Mitra, Amit K IR - Mitra AK FIR - Mishra, Shrawan K IR - Mishra SK FIR - Pasha, Qadar IR - Pasha Q FIR - Sivasubbu, Sridhar IR - Sivasubbu S FIR - Pandey, Rajesh IR - Pandey R FIR - Baral, Aradhita IR - Baral A FIR - Singh, Prashant K IR - Singh PK FIR - Sharma, Amitabh IR - Sharma A FIR - Kumar, Jitender IR - Kumar J FIR - Stobdan, Tsering IR - Stobdan T FIR - 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Verma R FIR - Sudheer, G IR - Sudheer G FIR - Mahajan, Anubha IR - Mahajan A FIR - Chavali, Sreenivas IR - Chavali S FIR - Tabassum, Rubina IR - Tabassum R FIR - Grover, Sandeep IR - Grover S FIR - Gupta, Meenal IR - Gupta M FIR - Batra, Jyotsna IR - Batra J FIR - Kumar, Amrendra IR - Kumar A FIR - Nejatizadeh, Abdoulazim IR - Nejatizadeh A FIR - Vaid, Mudit IR - Vaid M FIR - Das, Swapan K IR - Das SK FIR - Sharma, Shilpy IR - Sharma S FIR - Sharma, Mamta IR - Sharma M FIR - Chatterjee, Rajshekhar IR - Chatterjee R FIR - Paul, Jinny A IR - Paul JA FIR - Srivastava, Pragya IR - Srivastava P FIR - Rajput, Charu IR - Rajput C FIR - Mittal, Uma IR - Mittal U FIR - Singh, Mridula IR - Singh M FIR - Hariharan, Manoj IR - Hariharan M FIR - Das, Sumantra IR - Das S FIR - Chaudhuri, Keya IR - Chaudhuri K FIR - Sengupta, Mainak IR - Sengupta M FIR - Acharya, Moulinath IR - Acharya M FIR - Bhattacharyya, Ashima IR - Bhattacharyya A FIR - Saha, Atreyee IR - Saha A FIR - Biswas, Arindam IR - Biswas A FIR - Chaki, Moumita IR - Chaki M FIR - Gupta, Arnab IR - Gupta A FIR - Mukherjee, Saibal IR - Mukherjee S FIR - Mookherjee, Suddhasil IR - Mookherjee S FIR - Chattopadhyay, Ishita IR - Chattopadhyay I FIR - Banerjee, Taraswi IR - Banerjee T FIR - Chakravorty, Meenakshi IR - Chakravorty M FIR - Misra, Chaitali IR - Misra C FIR - Monadal, Gourish IR - Monadal G FIR - Sengupta, Shiladitya IR - Sengupta S FIR - De, Dipanjana Dutta IR - De DD FIR - Bajaj, Swati IR - Bajaj S FIR - Deb, Ishani IR - Deb I FIR - Banerjee, Arunava IR - Banerjee A FIR - Chowdhury, Rajdeep IR - Chowdhury R FIR - Banerjee, Debalina IR - Banerjee D FIR - Kumar, Deepak IR - Kumar D FIR - Das, Sumit Ranjan IR - Das SR FIR - Tiwari, Shrish IR - Tiwari S FIR - Bharadwaj, Anshu IR - Bharadwaj A FIR - Khanna, Sangeeta IR - Khanna S FIR - Ahmed, Ikhlak IR - Ahmed I FIR - Parveen, Sumera IR - Parveen S FIR - Singh, Nivedita IR - Singh N FIR - Dasgupta, Dipayan IR - Dasgupta D FIR - Bisht, Siddharth Singh IR - Bisht SS FIR - Rajput, Rashmi IR - Rajput R FIR - Ghosh, Biswaroop IR - Ghosh B FIR - Kumar, Naveen IR - Kumar N FIR - Chaurasia, Amit IR - Chaurasia A FIR - Abraham, James K IR - Abraham JK FIR - Sinha, Amit IR - Sinha A FIR - Scaria, Vinod IR - Scaria V FIR - Sethi, Tav Pritesh IR - Sethi TP FIR - Mandal, Amit K IR - Mandal AK FIR - Mukhopadhyay, Arijit IR - Mukhopadhyay A EDAT- 2012/06/23 06:00 MHDA- 2012/12/10 06:00 CRDT- 2012/06/23 06:00 PHST- 2012/06/23 06:00 [entrez] PHST- 2012/06/23 06:00 [pubmed] PHST- 2012/12/10 06:00 [medline] AID - jc.2012-1328 [pii] AID - 10.1210/jc.2012-1328 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2012 Sep;97(9):E1820-4. doi: 10.1210/jc.2012-1328. Epub 2012 Jun 20.