To investigate association of two LPIN1 gene variations with main traits of metabolic syndrome (MS) (waist circumference, body mass index, blood pressure, triglycerides, HDL-cholesterol and fasting ...glucose levels) in population from Bosnia and Herzegovina.
This study included 43 patients with metabolic syndrome and 43 healthy controls from General Hospital in Tešanj, Bosnia and Herzegovina. Subjects were genotyped for two LPIN1 gene variations (rs11693809: C>T and rs2716610: C>T) by real time PCR method.
In control subjects LPIN1 polymorphism, rs2716610: C>T, was significantly associated with a lower body mass index (BMI) (p=0.008) and waist circumference (p=0.008). The second analyzed rs11693809: C>T polymorphism was associated with lower blood HbA1c levels (p=0.048) in a group of MS patients.
Results of our study suggest that rs2716610: C>T polymorphism of LPIN1 gene could have a protective effect against development of metabolic syndrome, while rs11693809: C>T might affect a glucose control in patients with MS.
Introduction: Gilbert’s syndrome is the most common hereditary disorder of bilirubin metabolism. The causative mutation in Caucasians is almost exclusively a (TA) dinucleotide insertion in the UGT1A1 ...promoter. Affected individuals are homozygous for the variant promoter and have 7 TA repeats in-stead of 6. Promoters with 5 and 8 TA repeats also exist but are extremely rare in Caucasians. The aim of our study was to develop denaturing high-performance liquid chromatography (DHPLC) assay for genotyping UGT1A1(TA)n polymorphism and to compare it with a previously described single-strand conformation polymorphism (SSCP) assay.
Materials and methods: Fifty DNA samples with common genotypes ((TA)6/6, (TA)6/7, (TA)7/7) as well as 7 samples with one of the following rare genotypes - (TA)5/6, (TA)5/7, (TA)6/8 or (TA)7/8 were amplifi-ed by polymerase chain reaction (PCR) and genotyped by DHPLC using sizing mode. All samples were previously genotyped by SSCP assay which was validated by sequencing analysis.
Results: All samples with either common or rare genotypes showed completely concordant results between DHPLC and SSCP assays. Our results show that sizing DHPLC assay is more efficient compared to classical SSCP assay due to shorter time of genotyping analysis, ability of genotyping increased number of samples per day, higher robustness, reproducibility and cost-effectiveness with no loss of accuracy in detection of all UGT1A1(TA)n genotypes.
Conclusions: We developed a new DHPLC assay which is suitable for accurate, automated, highthroughput, robust genotyping of all UGT1A1(TA)n polymorphism variants, compared to a labour intensive and time-consuming SSCP assay.
ntroduction: The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the con-version of the hormonally inactive cortisone to active cortisol, thus facilitating glucocorticoid receptor ...activation in target tissues. Increased expression of 11β-HSD1 in adipose tissue has been associated with obesity and insulin resistance. In this study, we investigated the association of two 11β-HSD1 gene (HSD11B1) polymorphisms with the metabolic syndrome (MetS) and its characteristics in the Bosnian population.
Materials and methods: The study included 86 participants: 43 patients diagnosed with MetS and 43 healthy controls. Subjects were genotyped for two HSD11B1 gene polymorphisms: rs846910: G>A and rs45487298: insA, by the high resolution melting curve analysis. Genotype distribution and an influence of genotypes on clinical and biochemical parameters were assessed.
Results: There was no significant difference in the mutated allele frequencies for the two HSD11B1 gene polymorphisms between MetS patients and controls. In MetS patients, no significant associati-ons between disease-associated traits and rs45487298: insA were found. Regarding rs846910: G>A variant, heterozygous patients (G/A) had significantly lower systolic (P = 0.017) and diastolic blood pressure (P = 0.015), lower HOMA-IR index (P = 0.011) and higher LDL-cholesterol levels (P = 0.049), compared to the wild-type homozygotes. In the control group, rs45487298: insA polymorphism was associated with lower fasting plasma insulin levels (P = 0.041), lower homeostasis model asses-sment insulin resistance (HOMA-IR) index (P = 0.041) and lower diastolic blood pressure (P = 0.048). Significant differences between rs846910: G>A genotypes in controls were not detected. Haplotype analysis confirmed the association of rs45487298: insA with markers of insulin resistance in the con-trol subjects.
Conclusions: Our results indicate that a common rs45487298: insA polymorphism in HSD11B1 gene may have a protective effect against insulin resistance.
Clonal expansion of CD4+CD28- T cells is a characteristic finding in patients with rheumatoid arthritis (RA). Expanded CD4+ clonotypes are present in the peripheral blood, infiltrate into the joints, ...and persist for years. CD4+CD28- T cells are oligoclonal lymphocytes that are rare in healthy individuals but are found in high percentages in patients with chronic inflammatory diseases. The size of the peripheral blood CD4+CD28- T-cell compartment was determined in 42 patients with RA and 24 healthy subjects by two-color FACS analysis. The frequency of CD4+CD28- T cells was significantly higher in RA patients than in healthy subjects. Additionally, the number of these cells was significantly higher in patients with extra-articular manifestations and advanced joint destruction than in patients with limited joint manifestations. The results suggest that the frequency of CD4+CD28- T cells may be a marker correlating with extra-articular manifestations and joint involvement.
Objectives
Acetylation polymorphism can alter therapeutic responses and toxicity to certain xenobiotics and may also be a factor that influences a patient's susceptibility to certain diseases. We ...investigated whether patients with rheumatoid arthritis (RA) differed from healthy individuals with regard to genotype of the polymorphic enzyme N‐acetyltransferase 2 (NAT2).
Methods
NAT2 polymorphism was compared in 118 healthy subjects and 82 patients with RA. NAT2 alleles (*4, *5, *6, and *7) were determined by polymerase chain reaction‐restriction fragment length polymorphism methods with deoxyribonucleic acid extracted from peripheral blood.
Results
A statistically significant increase in the proportion of homozygous slow acetylators with 2 mutated alleles (84.1%) was found among patients with RA in comparison with healthy subjects (52.5%; P < .0001). The risk of development of RA was almost 5‐fold greater in slow acetylators than in fast acetylators (odds ratio, 4.79; 95% confidence interval, 2.28–10.21). There was no correlation between NAT2 polymorphism and presence of rheumatoid factor, extra‐articular manifestations, and age at first occurrence of disease symptoms.
Conclusions
NAT2 slow acetylation genotype may be a risk factor of individual susceptibility to RA.
Clinical Pharmacology & Therapeutics (2002) 72, 319–325; doi: 10.1067/mcp.2002.126740
Chronic inflammatory syndromes such as rheumatoid arthritis (RA) are associated with high frequencies of CD4+CD28- T cells. The number of these cells is genetically determined and may also be a ...consequence of chronic exposure to tumor necrosis factor-alpha (TNFalpha). The aim of this study was to examine whether the reported efficacy of anti-TNFalpha therapy in RA involves a resurgence of T cell populations that re-express CD28. After 36-week therapy with infliximab, a significant decrease in CD4+CD28- T cells in RA patients was observed in comparison with baseline. The results suggest that TNFalpha-neutralizing therapy may restore T cell homeostasis and reduce expansion of the CD28- T cells, which are cytotoxic and may contribute to organ manifestations in RA.
Rheumatoid arthritis is a systemic disease that causes inflammation and joint destruction. As a result of pathological destruction in bone and cartilage, crosslinks in collagen are resorbed more ...rapidly. This causes a rise in circulating collagen crosslink levels and their urinary excretion. In RA, apart from the crosslink resorption at the site of inflamed joints, there may be increased resorption due to general bone loss associated with disease activity. The aim of this study was to evaluate the influence of therapy with infliximab on urinary excretion of pyridinoline (PYD) and deoxypyridinoline (DPYR) as a markers of collagen degradation and its correlation with clinical and biochemical parameters of disease activity. Seventeen patients with active rheumatoid arthritis treated with infliximab were recruited into the study. The therapy resulted in the reduction in the symptoms of RA and urinary excretion of PYD and DPYR. The urinary excretion of PYD correlated with a number of swollen joints, morning stiffness, CRP and ESR. The urinary excretion of DPYR correlated during infliximab therapy with the number of swollen and tender joints and morning stiffness. The measurement of urinary excretion of PYR and DPYR may give insight into bone metabolism and help us to better understand the actual changes in bone and cartilage caused by RA and its treatment.
Polymorphism of phagocyte IgG receptor Fc gamma RIIa may modulate immune complex mediated inflammation, particularly when immune complex contain IgG2.
Fc gamma RIIa genotyping in 82 patients with ...rheumatoid arthritis (RA) and 148 healthy subjects was performed using the polymerase chain reaction technique with allele specific primers.
No significant relation between Fc gamma RIIa genotypes and susceptibility to RA was observed, but extraarticular complications with high frequency were revealed in patients with R/R131 genotype.
The results suggest that the Fc gamma RIIa polymorphism is not a risk factor for RA.
Antiphospholipd syndrome (APS) is a disease characterised by venous and arterial thrombosis or recurrent foetal loss, which are associated with antiphospholipid antibodies or/and lupus anticoagulant. ...Clinical symptoms ofAPS are assocciated with presence of noninflammatory thrombosis ocluding arteries or venes. Symptoms of APS are often very dramatic what can be illustrated by the presented case of 40 year patient. At the age of 25 after a miscarriage the patient developed tetraparesis and motor aphasia in the course of thrombosis in central nervous system vessels. In physical examination besides neurological symptoms reticular livedo was found on the trunk and limbs. Serological tests have revealed presence of high titre of IgG and IgM anticardiolipin antibodies and lupus anticoagulant (LA). CT examination revealed hypodensic foci in left parietal lobe, and abnormal EEG findings were observed in fronto-temporal leads of left hemisphera of brain. At that point the patient did not meet the criteria of connective tissue diseases, including lupus. The diagnosis of primary APS was suggested. The patient received anti-aggregation treatment and also immunosuppressive drugs (azathioprine and prednison) due to progression of neurological manifestations. 3 years later, the second pregnancy ended in the 27th week with intrauterine fetal death. During the 3rd pregnancy, 2 years afterwards, the patient was treated with heparin, aspirin and intravenous immunoglobulin. The pregnancy finished with a successful delivery at term, the newborn was in good condition. During the following pregnancy the symptoms of preeclampsia occurred at 36/37th week but the newborn was delivered in a good condition after a caesarean section. At the age of 36 patient developed ischemic brain stroke with left-side hemiparesis inspite of anti-aggregation and immunosupressive (prednison and azathioprine) treatment. At that time homogenic type antinuclear antibodies (ANA) 1:2560, anti-beta2-glycoprotein antibodies (beta2-GPI), aCL antibodies in medium titer and thrombocytopenia were found. The patient was treated with heparin, cyclophosphamide and methyloprednisolon intravenously. During rehabilitation process gradual improvement of cognitive functions, speech and motorical functions was observed. Recently high titre of ANA and recurent thrombocytopenia < 100,000/mm3 were present. Maybe during the further follow-up, 14 years after the first symptoms of APS, the patient will develop full blown symptoms of SLE.
The FcgammaRIIa receptor is most widely distributed of the Fcgamma receptors and is expressed on the most types of immunocomponent cells. Polymorphism of the FcgammaRIIa receptors may modulate immune ...complex mediated inflammation, particularly when immune complex contains IgG. The aim of the study was to evaluate the influence the FcgammaRIIa polymorphism on disease parameters activity in patients with rheumatoid arthritis (RA). The study included 75 patients with RA diagnosed according to the American College of Rheumatology criteria. In each patient the following parameters of disease activity were evaluated during one-year period: number of swollen and tender joints, morning stiffness duration, CRP, ESR as well as the disease activity in global physical assessment. There was no correlation between disease activity parameters and FcgammaRIIa polymorphism. Our results suggest, that FcgammaRIIa polymorphism does not represent an important genetic risk factor for RA activity.
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