Association of HLA-G 3‿untranslated region variants with type 1 diabetes mellitus

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• 作者：Rafael S. de Albuquerque^a ; ^b ; Celso Teixeira Mendes-Junior^c ; ^{ctmendes@ffclrp.usp.br" class="auth_mail" title="E-mail the corresponding author} ; Norma Lucena-Silva^d ; Camila Leal Lopes da Silva^c ; Diane Meire Rassi^e ; Luciana C. Veiga-Castelli^e ; Maria Cristina Foss-Freitas^e ; Milton Cé ; sar Foss^e ; Neifi Hassan Saloum Deghaide^e ; Philippe Moreau^f ; Silvia Gregori^b ; Erick C. Castelli^g ; Eduardo Antô ; nio Donadi^e
• 关键词：T1D ; Type 1 diabetes mellitus ; 3&prime ; UTR ; 3&prime ; untranslated region ; SNP ; single nucleotide polymorphism ; MHC ; major histocompatibility complex ; HLA ; human leukocyte antigen ; NK ; natural killer ; CTL ; cytotoxic T lymphocytes ; HWE ; Hardy&ndash ; Weinberg equilibrium ; EM ; expectation-maximization ; 5&prime ; URR ; promoter ; LD ; linkage disequilibrium
• 刊名：Human Immunology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：77
• 期：4
• 页码：358-364
• 全文大小：375 K

文摘

Besides the well recognized association of HLA-DRB1 and DQB1 alleles with type 1 diabetes mellitus (T1D), linkage studies have identified a gene region close to the non-classical class I HLA-G gene as an independent susceptibility marker. HLA-G is constitutively expressed in the endocrine compartment of the human pancreas and may play a role in controlling autoimmune responses. We evaluated the genetic diversity of the 3′ untranslated region (3′UTR) of HLA-G, which have been associated with HLA-G mRNA post-transcriptional regulation, in 120 Brazilian T1D patients and in 120 healthy controls. We found the +3001 T allele was observed only in T1D patients. Notably, the +3001 T allele was in linkage disequilibrium with polymorphic sites associated with low production of HLA-G mRNA or soluble HLA-G levels. Moreover, T1D patients showed a low frequency of the HLA-G 3′UTR-17 (14bpINS/+3001T/+3003T/+3010C/+3027C/+3035T/+3142G/+3187A/+3196C). The +3010 CC genotype and the UTR-3 haplotype (14bpDEL/+3001C/+3003T/+3010C/+3027C/+3035C/+3142G/+3187A/+3196C), associated with low and moderate soluble HLA-G expression, respectively, were underrepresented in patients. The decreased expression of HLA-G at the pancreas level should be detrimental in individuals genetically prone to produce less HLA-G.