Endothelial nitric oxide synthase polymorphisms in biopsy-proven erythema nodosum from a defined population

OBJECTIVE: To assess the potential in-fluence of endothelial nitric oxide synthase (eNOS) polymorphisms in the susceptibility to and clinical expression of a series of patients diagnosed with biopsy-proven erythema nodosum (EN). METHODS: Ninety-seven unselected patients from Northwest Spain with biopsy-proven EN were studied. Patients and ethnically matched controls were genotyped by PCR based techniques for a variable number tandem repeat polymorphism in intron 4, a T/C polymorphism at position -786 in the promoter region and a polymorphism in exon 7 (298Glu/Asp or 5557G/T) of the eNOS gene. RESULTS: No differences in allele or genotype frequencies for any of the individual eNOS polymorphisms were observed between biopsy-proven patients with EN and controls. It was also the case when patients with EN secondary to sarcoidosis were compared with the remaining patients or controls. In the group of patients with EN, no linkage disequilibrium between these polymorphisms was found. Also, no significant differences in haplotype frequencies were observed between patients and controls. CONCLUSION: Our present results do not support a role for eNOS polymorphisms in the susceptibility to and clinical expression of EN.     

Lack of association between intercellular adhesion molecule-1 gene polymorphisms and giant cell arteritis

OBJECTIVE: Studies have shown an association between HLA-DRB1*04 and giant cell arteritis (GCA). Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms were reported to contribute susceptibility to GCA in Italian patients where susceptibility to GCA is not associated with HLA-DRB1*04 alleles. ICAM-1 is also highly expressed within inflammatory infiltrates of the blood vessels of GCA patients. To investigate the clinical implications of ICAM-1 polymorphisms in GCA, we examined their potential association and influence in the development of visual ischemic complications in a series of patients with GCA from Northwest Spain where GCA susceptibility is associated with HLA-DRB1*04. METHODS: Fifty-eight biopsy proven GCA and 129 ethnically matched controls were studied. Patients and controls were genotyped for ICAM-1 polymorphism at codons 241 and 469 by PCR-RFLP. RESULTS: The distribution of the alleles and genotypes for each ICAM- polymorphism did not show significant differences between GCA patients and controls. Although visual manifestations were significantly more likely to occur in men than women (OR 5.2, p = 0.018), allele and genotype frequencies of ICAM-1 polymorphisms in patients with GCA were not associated with development of visual complications or anemia. Visual complications in GCA were primarily associated with carriage of an HLA-DRB1*04 allele. No evidence was found for interaction between HLA-DRB1*04 and ICAM-1 polymorphism. CONCLUSION: ICAM-1 polymorphisms are not genetic risk factors for the susceptibility and severity of GCA in Northwest Spain.     

Lack of association between interleukin 23 receptor gene polymorphisms and rheumatoid arthritis susceptibility

The recent discovery of interleukin 23 (IL-23), its receptor, and the underlying signal transduction pathway has improved our understanding of cellular immunity. Several studies suggest that IL-23 is an essential promoter of chronic joint inflammation. In this report, we assess the possible association of interleukin 23 receptor (IL23R) polymorphisms and haplotypes with rheumatoid arthritis (RA). The study was conducted on 1,204 RA patients and 979 healthy controls. Seven polymorphisms were selected from previous IBD reports. The seven SNPs (rs1004819, rs7517847, rs10489629, rs2201841, rs1343151, rs11209032 and rs1495965) were genotyped using the TaqMan assay. Comparison of RA and control subjects revealed no statistically significant differences in the distribution of the IL23R genotypes and haplotypes. Our results clearly indicate that IL23R gene polymorphisms do not play a significant role in susceptibility to RA in the Korean population. Accordingly, we conclude that IL23R gene polymorphisms cannot be applied as an effective genetic marker for RA susceptibility.     

Lack of association between thyrotropin receptor gene polymorphisms and subclinical hypothyroidism in children

Subclinical hypothyroidism is defined as a serum TSH level above the statistically set reference range, associated to normal free thyroid hormone concentrations. Genetic and environmental factors contribute to the inter- and intra-individual biological variations of TSH levels, sometimes leading to uncertainty of treatment in the clinical practice, especially when moderate elevations above the upper limit of the reference range are considered (5< TSH <10 mIU/l). In this view, the study of association between subclinical hypothyroidism and possible molecular effectors, such as polymorphisms in the TSH receptor (TSHR) gene, could be interesting. In this paper, we analyzed the TSHR gene polymorphisms in 103 hyperthyrotropinemic infants. A control group of 120 newborns of the same ethnic background was used to evaluate the frequencies of each polymorphism in the population. We found a statistically significant difference in the allelic frequency of the P52T polymorphism, being that the T variant was more represented in the control group (p=0.03). However, no significant results have been obtained in the analysis of the association between genotypes and serum TSH levels. In conclusion, we analyzed 7 polymorphic variants of TSHR gene in subclinical hypothyroidism. The only significant result refers to the allelic frequency of A in the P52T polymorphism, which is statistically reduced when compared with that of a control group.     

Lack of association between transforming growth factor-beta1 gene polymorphisms and mitral valve prolapse in Taiwan Chinese

BACKGROUND AND AIMS OF THE STUDY: A role of collagen abnormality in the pathogenesis of mitral valve prolapse (MVP) has been addressed. It is considered that transforming growth factor-beta1 (TGF-beta1) may be responsible for the increased deposition of extracellular matrix in hypertensive blood vessels, and increased myocardial collagen expression and myocardial fibrosis in human aortic valve disease. However, the role of a TGF-beta1 genetic variant in MVP has not been studied. Hence, a case-controlled study was carried out to investigate the possible relationship between the TGF-beta1 gene C-509T and T869C polymorphisms and MVP among the Chinese population in Taiwan. METHODS: A group of 100 patients with MVP diagnosed by echocardiography, and 100 age- and sex-matched normal control subjects were studied. TGF-beta1 gene polymorphisms C-509T and T869C were identified by polymerase chain reaction-based restriction analysis. RESULTS: There was no significant difference in the distribution of TGF-beta1 C-509T genotypes (p = 0.76) and allelic frequencies (p = 0.69) between MVP cases and controls; neither was any significant difference seen in the distribution of TGF-beta1 T869C genotypes (p = 0.95) and allelic frequencies (p = 0.84) between MVP cases and controls. Further categorization of MVP patients into mild and severe subgroups also revealed no statistical difference in C-509T and T869C polymorphisms of the TGF-beta1 gene compared with controls. CONCLUSION: These findings suggest that the C-509T and T869C polymorphisms of the TGF-beta1 gene are not suitable genetic markers of MVP in Taiwan Chinese.     

Lack of association between UCP2 gene polymorphisms and obesity phenotype in Italian Caucasians

The importance of the genetic component on adipose tissue accumulation has been clearly demonstrated. Among the candidate genes investigated, there are those that regulate thermogenesis and, thus, can affect energy expenditure. The uncoupling proteins (UCPs) are a family of proteins that uncouple respiration leading to generation of heat and increased energy expenditure. Contradictory data indicate that allelic variants in their coding genes might be associated with obesity. In this study we evaluated the role of two allelic variants of the UCP2 gene in obesity and the association with its sub-phenotypic characteristics. To this aim, 360 morbidly obese patients [age: 45 +/- 15 yr, body mass index (BMI): 46 +/- 7 kg/m2] and 103 normal weight subjects (BMI < 24 kg/m2) were genotyped for the 45 bais-pair (bp) insertion/deletion (I/D) in the 3'-untraslated region of exon 8 of the UCP2 gene while the presence of an Ala/Val substitution at codon 55 (Ala55Val) of the same gene was studied in 104 obese and 50 lean subjects. Patients also underwent a study protocol including measurements of BMI, waist-to-hip ratio (WHR), resting energy expenditure (REE), energy intake, fat mass (FM) and free fat mass (FFM), total cholesterol (TCH), high density lipoprotein (HDL) cholesterol, triacylglyceroles (TG), leptin levels, basal glucose, immunoreactive insulin (IRI), glycated haemoglobin (HbA1c), insulin sensitivity and thyroid hormones. No significant association between the two polymorphisms studied and the clinical, metabolic and anthropometric parameters characteristic of the obese phenotype was found. These results, in accordance with similar findings previously obtained in other ethnic groups, suggest that these two UCP2 allelic variants may not have a direct role in the pathogenesis and development of obesity.     

Lack of association between IL-6 gene polymorphisms and rheumatoid arthritis in Turkish population

Inflammatory cytokines play an important role in the pathogenesis of rheumatoid arthritis (RA). One of candidate genes is interleukin-6 (IL-6), and single-nucleotide polymorphisms in the promoter region of IL-6 were found to be associated with RA. The aim of this study was to determine the association between IL-6 promoter polymorphisms (-174, -572, -597) and RA in Turkish population. A total of 425 subjects were recruited into the study (247 healthy controls and 178 RA). The promoter region of IL-6 gene was amplified by PCR using DNAs from patients and the controls, and their PCR products were digested by suitable enzymes. No significant association was found between RA and -174 genotype distribution (P = 0.535) and allele frequency (P = 0.230). There was also no relationship between -572 (P = 0.150) and -597 (P = 0.912) gene polymorphism and RA. Our results suggested that IL-6 gene promoter polymorphisms have no association with RA in Turkish population.     

Lack of association between -384 and 114 IL-2 gene polymorphisms and rheumatoid arthritis

OBJECTIVE: To investigate the association of 2 single nucleotide polymorphisms (SNP) at positions -384 and 114 in the human interleukin 2 (IL-2) gene with susceptibility to and severity of rheumatoid arthritis (RA). METHODS: Genotyping for these IL-2 variants was performed by a polymerase chain reaction restriction fragment length polymorphism method in 174 RA patients and 153 control individuals. RESULTS: No statistically significant differences were observed when the -384 and 114 IL-2 genotype distributions between RA patients and healthy controls were compared. In addition, no association was found between the IL-2 genotypes with any demographic and clinical variables tested. CONCLUSION: Our results provide no evidence for genetic association conferred by the -384 and 114 IL-2 SNP with respect to susceptibility and severity of RA.     

Lack of association between interleukin-4 gene polymorphisms and autoimmune thyroid diseases amongst Taiwanese Chinese

Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) are both common autoimmune diseases of the thyroid gland (AITD). The IL-4 is involved in both humoral and cellular immunity. The aim of this study was to test whether the IL-4 gene could be used as a genetic marker to predict the development of AITD amongst the Chinese population of Taiwan. For this study, a normal control group of 105 healthy subjects and two experimental groups featuring individuals afflicted with either GD (104 patients) or HT (109 patients) were examined. Polymerase chain reaction (PCR) was used to analyze the variable number of tandem repeats (VNTRs) polymorphism for the IL-4 gene intron 3 and PCR-based restriction analysis using endonuclease BsmFI was undertaken for the same gene at the promoter −590 position. We found no significant difference in the frequencies of presence of genotype and allelic variants for the IL-4 gene at both the intron 3 and the promoter regions between the normal control group and each of the two patient groups. These findings suggest that the IL-4 gene polymorphisms that arise at either intron 3 or promoter −590 positions are not suitable genetic markers for AITD among Taiwanese Chinese.     

Lack of association between scleroderma and types I and III procollagen gene restriction fragment length polymorphisms

Restriction fragment length polymorphisms (RFLPs) in types I and III procollagen genes were studied in 62 scleroderma patients and 138 healthy controls. Allelic frequencies were determined for each RFLP, and comparisons were made between the 2 populations, stratifying them by race when appropriate. No statistically significant differences were observed for the frequencies of any of the RFLPs studied.     

Lack of association with interleukin 1 receptor antagonist and interleukin-1beta gene polymorphisms in sarcoidosis patients

Interleukin-1beta (IL-1beta) and its endogenous antagonist, the interleukin-1 receptor antagonist (IL-1ra), play important roles in immune responses. In sarcoidosis, IL-1beta is reported to be increased whereas IL-1ra is decreased. It has recently been shown that polymorphisms in the IL-1ra and IL-1beta genes may account for variation in the two proteins. These polymorphisms are also reported to be associated with several autoimmune diseases. Since this might be expected to affect sarcoidosis, an investigation of 108 sarcoidosis patients and 113 healthy control subjects was performed. The IL-1ra genotype was determined using the polymerase chain reaction (PCR), and the IL-1beta genotype by PCR restriction fragment length polymorphism. We found no significant differences in IL-ra and IL-1beta genotypes between sarcoidosis patients and healthy controls. Furthermore, there was no association between the IL-1beta genotype and the roentgenographic stage, disappearance of chest X-ray shadows or organ involvement. In conclusion, there is no bias in the IL-1ra and IL-1beta genotype in Japanese sarcoidosis patients.     

Lack of association between connexin40 polymorphisms and coronary artery disease

BackgroundMacrocytosis, as a qualitative abnormality of erythrocytes, has not drawn attention as a prognostic indicator after PCI, while anemia, as a quantitative abnormality of erythrocytes, has been recognized as a predictor of adverse outcomes. The aim of this study was to perform prognostic risk stratification of patients after PCI based on the presence or absence of macrocytosis.MethodsThe clinical records of 941 consecutive patients who underwent PCI at a single institution were retrospectively reviewed. The prognostic implication of macrocytosis was evaluated by univariate and multivariate Cox's proportional hazard regression analysis.ResultsThere were 130 (13.8%) patients with macrocytosis. A significantly higher all-cause and cardiac mortality, as well as incidence of composite adverse events were observed in the Macrocytic group. Kaplan–Meier analysis also showed a significantly poorer overall survival in patients with macrocytosis. Even after exclusion of anemic patients, this tendency was still observed. Furthermore, macrocytosis was significantly and independently associated with adverse outcomes after PCI (aHR of cardiac death: 3.45, 95%CI: 1.22–9.80, P = 0.019). Interestingly, fewer patients with macrocytosis were prescribed statins compared with those without it (33.8% vs. 47.1%, P = 0.005).ConclusionsThe results of the study indicate that measuring mean corpuscular volume (MCV) as a qualitative index of erythrocytes might be helpful for a prognostic risk stratification of patients subjected to PCI.     

Lack of an association between interleukin-12 receptor beta1 polymorphisms and tuberculosis in Koreans

BACKGROUND: The fact that only 10% of people infected with Mycobacterium tuberculosis develop clinical tuberculosis (TB) suggests the presence of genetic factors in the pathogenesis of TB. To date, a number of single nucleotide polymorphisms (SNPs) in several candidate genes have been proposed as genetic risk factors of TB; however, reports are conflicting. OBJECTIVES: We investigated whether SNPs in the interleukin (IL)-12 receptor beta1 gene are associated with TB in Koreans. METHODS: One hundred and fifteen patients with bacteriologically or pathologically confirmed TB and 151 healthy anonymous blood donors were enrolled. The genotypes of 5 SNPs on IL-12 receptor beta1 gene, +705A/G (Q214R), +1158T/C (M365T), +1196G/C (G378R), +1637G/A (A525T) and +1664 C/T (P534S), were determined by PCR-RFLP. RESULTS: No difference was observed between TB patients and controls in terms of the genotype frequencies of the 5 SNPs of the IL-12 receptor beta1 gene or of their haplotypes. CONCLUSIONS: In view of the finding that these SNPs have been reported to be associated with TB in the Japanese and Moroccan populations, our results may reflect racial differences in genetic susceptibility to TB.