Differences in Gene-Gene Interactions in Graves’ Disease Patients Stratified by Age of Onset

Background

Graves’ disease (GD) is a complex disease in which genetic predisposition is modified by environmental factors. Each gene exerts limited effects on the development of autoimmune disease (OR = 1.2–1.5). An epidemiological study revealed that nearly 70% of the risk of developing inherited autoimmunological thyroid diseases (AITD) is the result of gene interactions. In the present study, we analyzed the effects of the interactions of multiple loci on the genetic predisposition to GD. The aim of our analyses was to identify pairs of genes that exhibit a multiplicative interaction effect.

Material and Methods

A total of 709 patients with GD were included in the study. The patients were stratified into more homogeneous groups depending on the age at time of GD onset: younger patients less than 30 years of age and older patients greater than 30 years of age. Association analyses were performed for genes that influence the development of GD: HLADRB1, PTPN22, CTLA4 and TSHR. The interactions among polymorphisms were analyzed using the multiple logistic regression and multifactor dimensionality reduction (MDR) methods.

Results

GD patients stratified by the age of onset differed in the allele frequencies of the HLADRB1*03 and 1858T polymorphisms of the PTPN22 gene (OR = 1.7, p = 0.003; OR = 1.49, p = 0.01, respectively). We evaluated the genetic interactions of four SNPs in a pairwise fashion with regard to disease risk. The coexistence of HLADRB1 with CTLA4 or HLADRB1 with PTPN22 exhibited interactions on more than additive levels (OR = 3.64, p = 0.002; OR = 4.20, p < 0.001, respectively). These results suggest that interactions between these pairs of genes contribute to the development of GD. MDR analysis confirmed these interactions.

Conclusion

In contrast to a single gene effect, we observed that interactions between the HLADRB1/PTPN22 and HLADRB1/CTLA4 genes more closely predicted the risk of GD onset in young patients.     

Effect of cadmium and Phytophthora infestans on polyamine levels in potato leaves

Changes in putrescine, spermidine and spermine concentrations in potato ( Solanum tuberosum L.) leaves stressed either with cadmium, with the fungal pathogen Phytophthora infestans Mont. (de Bary) or with both simultaneously were investigated. The leaves of two cultivars, Bintje and Bzura, respectively susceptible and resistant to P. infestans were examined. The level of of putrescine did not change under any stress conditions. Cadmium stress caused at least a 2-fold increase in spermidine and spermine concentrations in susceptible leaves. In resistant leaves there was a 4-fold increase in spermidine and a decrease in spermine. The pathogenic stress produced similar changes in polyamine concentrations, i. e. with differences between the cultivars. The double stress induced antagonistic alterations in the concentrations of spermidine and spermine.     

Free sterols,steryl esters,glucosides, acylated glucosides and water-soluble complexes in Calendula officinalis

In 3- and 14-day-old seedlings and in the leaves of Calendula officinalis the following sterols were identified: cholestanol, campestanol, stigmastanol, cholest-7-en-3-β-ol, 24-methylcholest-7-en-3β-ol, stigmast-7-en-3β-ol, cholesterol, campesterol, sitosterol, 24-methylcholesta-5,22-dien-3β-ol, 24-methylenecholesterol, stigmasterol and clerosterol. Sitosterol was predominant in young and stigmasterol in old tissues. Young tissues contained relatively more campesterol but in old tissues a C₂₈Δ^5,22 diene was present suggesting transformation of campesterol to its Δ^5,22 analog, similar to that of sitosterol to stigmasterol. All the identified sterols were present as free compounds and also in the steryl esters, glucosides, acylated glucosides and water-soluble complexes. The variations in the amounts of these fractions in the embryo axes and cotyledons of 3- and 14-day-old seedlings and the distribution of individual sterols among the fractions are discussed.     

The incorporation of mevalonate-[2-14C] into the sterol fractions of Calendula officinalis

The incorporation of mevalonate-[2-¹⁴C] into the free sterols, steryl esters, steryl glucosides, acylated steryl glucosides and water-soluble complexes was investigated and the sterols of each fraction were separated into stanols, Δ⁷ sterols, Δ⁵ sterols, stigmasterol, clerosterol and methylene-cholesterol. The stanols and Δ⁷ sterols were more strongly labelled in the steryl esters than in the free sterols. The Δ⁵ sterols and stigmasterol were more intensively labelled in the free sterols than in the steryl esters. All sterol types were more labelled in the steryl glycosides than in the acylated steryl glucosides. Stanols were probably formed from Δ⁷ or Δ⁵ precursors.     

Cytogenetical relationships between Rumex tuberosus,R. thyrsiflorus and R. acetosa and occurrence of polyploidy among their hybrids

Summary Reciprocal crosses were performed between Rumex tuberosus and two other taxa belonging to the Acetosa group: R. acetosa and R. thyrsiflorus. All three taxa are dioecious with the same chromosome numbers, XX + 12A, XYY+12A, but they differ from one another in the morphology of some autosomes. R. tuberosus and R. thyrsiflorus are similar in external morphology, while R. acetosa differs greatly from the other two taxa in external morphology as well as ecological characteristics.The F ₁ and F ₂ hybrids were fully vigorous and viable but their fertility was greatly reduced. Meiotic irregularities were observed in hybrids derived from all crosses. The most remarkable meiotic irregularity was diad formation after first meiotic division. The unreduced gametes derived from diads were responsible for the high frequency of polyploidy observed among the F ₂ hybrids. In the cross R. tuberosus × R. acetosa the whole F ₂ generation was tetraploid.It is concluded from the analysis performed that R. tuberosus, R. acetosa and R. thyrsiflorus are separate species, closely related to one another but already isolated by genetic and ecological barriers.     

Sixteen newH-2 haplotypes derived from wild mice

Wild mice captured in Texas, Scotland, Federal Republic of Germany, Denmark, Spain, Greece, Israel, Egypt, and Chile were mated to inbred strains and through successive backcross matings and H-2 typing lines homozygous for wild-derived H-2, haplotypes were established. The lines, which are neither congenic nor inbred, were then typed with antibodies defining known H-2 alleles at class I and class II loci. In addition, antisera were produced by the immunization of inbred strains with tissues of the new lines. Sixteen of the lines were characterized in this manner. The characterization resulted in the identification of 16 new H-2 haplotypes, 11 new K alleles, 10 new D alleles, and 21 new class I antigenic determinants, most of them of the private type. Most of the haplotypes represent natural recombinants sharing segments of the H-2 complex with previously identified haplotypes. A number of haplotypes are recombinants between the K and the A loci, which in genetic studies have proved difficult to separate. The lines, however, also provide evidence for preservation of blocks of genes in the H-2 complex, particularly in the class II region. Some of class I alleles previously found in wild mice from Michigan have now been found again in these mice. Several class II alleles of these lines appear to be the same as those found in inbred strains. Identical or nearly identical class I and class II alleles thus commonly occur in different populations. These findings strengthen the argument that in populations, H-2 alleles are relatively stable.     

The influence of negative ionization of the air on motor activity in Syrian hamsters (Masocricetus auratus Waterhouse) in light conditions

The motor activity of Syrian hamsters (Mesocricetus auratus Waterhouse) under the influence of negative ionization of the atmosphere applied for 10, 20 or 30 min per day was investigated. An ionizer with output of 14000 light negative ions per 1 cm³ of air was used. Studies carried out in the light phase of a 1212 h light/dark regime revealed a relation between the reaction of the animal and the time of day at which ionization was applied. Ionization for 20 or 30 min in the light phase decreased motor activity, while 10 min of ionization increased it compared to control animals. Ionization in the dark phase gave a more distinct rise in activity than that applied in the light phase for all three durations of ionization.This work was supported by RP-II-12 (A₁)-Investigations concerning regulation mechanisms of biorhythms by animals and humans in the basic conditions and under stress