Triglyceride level affecting shared susceptibility genes in metabolic syndrome and coronary artery disease.

Metabolic syndrome is characterized primarily by abdominal obesity, high triglyceride- and low HDL cholesterol levels, elevated blood pressure, and increased fasting glucose levels, which are often associated with coronary heart diseases. Several factors, such as physical inactivity, age, and several endocrine and genetic factors can increase the risk of the development of the disease. Gathered evidence shows, that metabolic syndrome is not only a risk factor for cardiovascular disease, but often both of them have the same shared susceptibility genes, as several genetic variants have shown a predisposition to both diseases. Due to the spread of robust genome wide association studies, the number of candidate genes in metabolic syndrome and coronary heart disease susceptibility increases very rapidly. From the growing spectrum of the genes influencing lipid metabolism (like the LPL; PPARA; APOE; APOAI/CIII/AIV genecluster and APOAS5), the current review focuses on shared susceptibility variants involved in triglyceride metabolism and consequently the effects on the circulating triglyceride levels. As the elevated levels of triglycerides can be associated with disease phenotypes, some of these SNPs can have susceptibility features in both metabolic syndrome and in coronary heart disease, thereby some of them can even represent a kind of susceptibility link between metabolic syndrome and coronary artery disease.

Triglyceride level modifying functional variants of GALTN2 and MLXIPL in patients with ischaemic stroke.

BACKGROUND: Recent genome-wide studies identified several genetic variants associated with blood lipid level alterations. Because affected lipid metabolism can confer risk to the development of ischaemic stroke, we studied three polymorphisms reportedly associated with triglyceride-level changes, rs17145738 and rs3812316 of the MLXIPL locus, and rs4846914 variant of GALNT2 gene in biobanked samples of patients with stroke. This pool of samples was previously investigated for haplotype tagging minor alleles of apolipoprotein A5 gene (T-1131C, T1259C, IVS3+G476A and C56G), and an association was found between the minor allele carriage and the triglyceride levels, and also these variants were found to confer risk to the development of stroke. METHODS: Here, a total of 467 patients with stroke, stratified as large vessel, small vessel and mixed stroke groups, and 156 control subjects were genotyped using PCR-RFLP methods. RESULTS: In the current study, we could not verify association of the variants analyzed either with triglyceride and total cholesterol levels or with the risk of ischaemic stroke susceptibility. CONCLUSIONS: The data presented here revealed differentiated risk nature of the triglyceride level modifying natural gene variants.

Functional variants of the interleukin-23 receptor gene in non-gastrointestinal autoimmune diseases.

Variants of the gene of the interleukin-23 receptor (IL23R) were first identified as susceptibility factors in association with inflammatory bowel diseases. Since then it became clear that different variants of the gene play also role in a number of other autoimmune diseases like psoriasis, rheumatoid arthritis, ankylosing spondylitis and multiple sclerosis while in others, like systemic sclerosis, systemic lupus erythematosus or Sjögren syndrome the same effect could not be seen. However, the results are very controversial both in terms of the various polymorphisms and also in population specificity. The aim of the current paper is to overview all available reports on IL23R gene polymorphisms in various autoimmune and inflammatory diseases and to try to give an explanation on the possible effect of the examined variants.

Variants of the IL23R gene are associated with ankylosing spondylitis but not with Sjögren syndrome in Hungarian population samples.

Recently, associations were found between several autoimmune diseases and functional variants of interleukin-23 receptor (IL23R) gene; here, we studied the possible association of nine polymorphisms of IL23R with ankylosing spondylitis (AS) and with Sjögren syndrome (SS). In our study, we genotyped groups of patients with AS (n = 206), SS (n = 156) and healthy controls (n = 235) for rs11805303, rs10889677, rs1004819, rs2201841, rs11209032, rs11209026, rs10489629, rs7517847 and rs7530511 variants using PCR-RFLP methods. We observed significant increase in the carriage of the T allele of rs11805303 and the A allele of rs1004189 in the AS group compared with the controls. For the rs10889677 variant, the prevalence of the AA genotype and for the rs2201841, the CC genotype showed a more than two-fold increase in the AS group compared with the controls. By contrast, the GA heterozygous genotype of rs11209026 variant showed a significant decrease in AS patients compared with controls. Haplotype analysis revealed association of four IL23R haplotypes with AS. There was no difference in the distribution of any of the examined IL23R variants between controls and SS patients. In conclusion, we confirmed the susceptibility or protective associations of IL23R polymorphisms with AS in a Hungarian population and first demonstrated the involvement of the rs11805303 intronic single nucleotide polymorphisms, which was tested so far only for other autoimmune diseases.

Functional variants of interleukin-23 receptor gene confer risk for rheumatoid arthritis but not for systemic sclerosis.

OBJECTIVES: Recently, an association was found between Crohn's disease and the interleukin-23 receptor (IL-23R) gene. Since the IL-23/IL-17 pathway is known to associate with other autoimmune diseases, including rheumatoid arthritis (RA) and systemic sclerosis (SSc), we hypothesised that IL-23R could be a shared susceptibility gene. METHODS: Groups of patients with rheumatoid arthritis (n = 412), systemic sclerosis (n = 224), Crohn's disease (n = 190) and healthy controls (n = 220) were genotyped for rs10889677 (exon-3'UTR C2370A), rs2201841, and rs1884444 variants; the first two have been shown to confer risk for Crohn's disease. RESULTS: We observed an increased prevalence of the homozygous rs10889677 AA and homozygous rs2201841 CC genotypes both in the Crohn's disease and in the RA groups as compared to the controls (12.1%, 11.9% vs 5.91%, p<0.05; and 13.2%, 13.1% vs 5.91%, p<0.05), but not in the SSc patients. Logistic regression analysis revealed that bearing these alleles represent risk for the development of rheumatoid arthritis (chi(2) = 5.58, p = 0.018, OR = 2.15, 95% CI 1.14-4.06 for rs10889677; and chi(2) = 7.45, p = 0.006, OR = 2.40, 95% CI 1.28-4.51 for rs2201841). The rs1884444 allele, which has been previously reported as neutral for development of Crohn's disease, was also found neutral for all studied groups in the present study. CONCLUSIONS: The data reported here provide direct evidence that some allelic variants or haplogroups of IL-23R represent independent risk factors for rheumatoid arthritis as well as Crohn's disease, but not for scleroderma.