Juvenile Idiopathic Arthritis Subtype- and Sex-specific Associations with Genetic Variants in the PSMA6/PSMC6/PSMA3 Gene Cluster

Abstract

We demonstrate for the first time evidence of a sex-specific association of PSMA6/PSMC6/PSMA3 genetic variants with subtypes of JIA and plasma proteasome concentrations. Theoretical models of the functional significance of allele substitutions are discussed.

Study of association between polymorphisms in the PSMB5 (rs11543947) and PSMA3 (rs2348071) genes and multiple sclerosis in Latvians

“…Both markers were found to be in HWE in controls (c 2 = 2.72; p > 0.05). Allele and genotype spectrums and distributions were found to be similar (P > 0.05) for the first (191 samples, [21,22]) and the second (114 newly collected samples) Latvian population studies for each marker. The data of both population studies were grouped and total control group of 305 samples was used for further analysis.…”

“…Genetic variations in the 14q11-24 genes encoding proteasomal subunits were implicated previously in susceptibility to autoimmunity, type 2 diabetes mellitus, cardio-vascular disorders, and population adaptation to environment [21,22]. It appears that there is a large potential for some of these mutations also to be associated with multiple sclerosis.…”

“…Detailed description of the subject groups is given in Table 1. Total control group of 305 samples were represented by the two independent sample sets including the previously characterized [21,22] first Latvian population study consisting of 191 samples and the second Latvian population study of 114 newly collected samples. Ethnic origin of the subjects was not recorded; all of them represent very mixed inhabitants of Riga, forming some «average» genotype for North-East Europe.…”

“…Ethnic origin of the subjects was not recorded; all of them represent very mixed inhabitants of Riga, forming some «average» genotype for North-East Europe. The data on the rs11543947 and rs2348071 allele and genotype frequencies in the first Latvian population sample set were extracted from [21,22] to be compared with the data on genetic diversity obtained for the second Latvian population study and then to be grouped providing a total control group of 305 healthy individuals. All controls were carefully assessed to exclude the diagnosis of any inflammatory disorders.…”

“…Genomic DNA was extracted from nucleated blood cells using a kit for the genomic DNA extraction («Fermentas», Lithuania) and from oral swabs using the salting out method [24]. The rs11543947 and rs2348071 genotyping technologies were the same as published previously [21,22] including primer sequences, basic PCR procedure and analyses of amplified and digested products. For quality control, the 16 randomly chosen samples per each marker were genotyped in duplicate in different experiments.…”