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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors, along with other investigators, postulate that viruses may be one of the causes of the syndrome of autism. Many diseases, especially those where a viral infection and autoimmunity is suspected, are being studied to determine whether an association with histocompatibility antigens (human leukocyte antigens--HLA) exists. The authors studied HLA in autism to see if a relationship exists. Twenty autistic children and their parents were HLA typed. The control group consisted of 575 potential donors for renal transplantation, 134 healthy subjects, and 48 persons of different families who married into one large family that had been HLA typed. The control subjects were from the same geographical area as the experimental subjects. Subjects were typed by a modification of the microlymphocytotoxicity tests of Terasaki and McCleland (1964). HLA-A2 was increased when compared to geographical controls, chi 2 = 5.020, p less than .05, and when compared to controls from the literature, chi 2 = 3.88, p less than .05. However, when chi 2 is corrected for the number of antigen specificities, significance is lost. No antigen was significantly increased in the mothers. HLA-A10 was significantly increased in the fathers, chi 2 = 5.947, p less than .02; however, significance did not remain after correction for the number of antigen specificities. These negative findings do not disprove an association because the numbers are so small. This small sample needs to be enlarged and replicated locally as well as in other geographical areas.
J Autism Dev Disord 1980 Mar
PMID:HLA and autism. 696 77

Previous research has revealed associations between autism and immune genes located in the human leukocyte antigen (HLA). To better understand which HLA genetic loci may be associated with autism, we compared the class I HLA-A and -B alleles in autistic probands with case control subjects from Caucasian families. The frequency of HLA-A2 alleles was significantly increased in autistic subjects compared with normal allelic frequencies from the National Marrow Donors Program (NMDP) (p = 0.0043 after allelic correction). The transmission disequilibrium test for the A2 allele revealed an increased frequency of inheritance for autistic children (p = 0.033). There were no significant associations of autism with HLA-B alleles; however, the A2-B44 and A2-B51 haplotypes were two times more frequent in autistic subjects. The association and linkage of the class I HLA-A2 allele with autism suggests its involvement in the etiology of autism. Possible roles are discussed for the HLA-A2 association in the presentation of microbial antigen within the central nervous system and/or in the establishment of synaptic and neuronal circuits in the developing brain.
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PMID:The association and linkage of the HLA-A2 class I allele with autism. 1672 Feb 16

The "common variant-common disease" hypothesis was proposed to explain diseases with strong inheritance. This model suggests that a genetic disease is the result of the combination of several common genetic variants. Common genetic variants are described as a 5% frequency differential between diseased vs. matched control populations. This theory was recently supported by an epidemiology paper stating that about 50% of genetic risk for autism resides in common variants. However, rare variants, rather than common variants, have been found in numerous genome wide genetic studies and many have concluded that the "common variant-common disease" hypothesis is incorrect. One interpretation is that rare variants are major contributors to genetic diseases and autism involves the interaction of many rare variants, especially in the brain. It is obvious there is much yet to be learned about autism genetics. Evidence has been mounting over the years indicating immune involvement in autism, particularly the HLA genes on chromosome 6 and KIR genes on chromosome 19. These two large multigene complexes have important immune functions and have been shown to interact to eliminate unwanted virally infected and malignant cells. HLA proteins have important functions in antigen presentation in adaptive immunity and specific epitopes on HLA class I proteins act as cognate ligands for KIR receptors in innate immunity. Data suggests that HLA alleles and KIR activating genes/haplotypes are common variants in different autism populations. For example, class I allele (HLA-A2 and HLA-G 14 bp-indel) frequencies are significantly increased by more than 5% over control populations (Table 2). The HLA-DR4 Class II and shared epitope frequencies are significantly above the control populations (Table 2). Three activating KIR genes: 3DS1, 2DS1, and 2DS2 have increased frequencies of 15, 22, and 14% in autism populations, respectively. There is a 6% increase in total activating KIR genes in autism over control subjects. And, more importantly there is a 12% increase in activating KIR genes and their cognate HLA alleles over control populations (Torres et al., 2012a). These data suggest the interaction of HLA ligand/KIR receptor pairs encoded on two different chromosomes is more significant as a ligand/receptor complex than separately in autism.
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PMID:Common Genetic Variants Found in HLA and KIR Immune Genes in Autism Spectrum Disorder. 2781 16