Association of toll-like receptor 9 gene polymorphism in Chinese patients with systemic lupus erythematosus in Taiwan.

The purpose of this study was to determine whether toll-like receptor 9 (TLR9) gene polymorphisms were markers of susceptibility to or severity of systemic lupus erythematosus (SLE) in Taiwanese patients. The study included 211 healthy individuals and 167 Chinese patients with SLE. Polymorphisms of TLR9 [rs2066807 and rs187084 (-1486 T/C)] were typed from genomic DNA. The genotypes, allelic frequencies, and carriage rates were compared between patients with SLE and control subjects. The relationship between allelic frequencies and clinical manifestations of 167 patients with SLE was evaluated. There was no statistically significant difference in TLR9 (rs2066807) gene polymorphism, allelic frequency, and carriage rate between the SLE and control groups. However, for the genotype of TLR9 -1486 T/C (rs187084) polymorphism, there was a statistically significant difference between the SLE and the control groups (P < 0.001, χ(2) = 15.9). Moreover, there was a significant association between the two groups in allelic frequency and carriage rate of the T allele (P < 0.001, χ(2) = 18.5 and P < 0.01, χ(2) = 8.06, respectively). We did not detect any association between the TLR9 genotype and the clinical or laboratory profiles in patients with SLE. The results suggest that the TLR9 -1486 T/C (rs187084), but not TLR9 (rs2066807), polymorphism is related to SLE in Taiwanese patients.

MBD4 gene is associated with rheumatoid arthritis in Chinese patients in Taiwan.

This study examines whether or not MBD4 polymorphism is a marker for rheumatoid arthritis (RA) susceptibility or severity for Chinese patients in Taiwan. This study included 193 patients with RA, while 190 unrelated healthy individuals living in Central Taiwan served as controls. The relationship between MBD4 polymorphism and clinical manifestations of RA was evaluated. For the genotype and allelic frequency of MBD4-1057 polymorphism, there were no statistically significant differences between patients with RA and controls. There were significant differences in the distribution of MBD4-8666 polymorphism frequencies between patients with RA and controls [P = 0.013; P (corrected) (Pc) = 0.039]. There were also significant relationships in the distribution of MBD4-9229 polymorphism genotype between patients with RA and controls (P = 0.007; Pc = 0.021). However, we did not detect any associations for MBD4-1057, MBD4-8666 or MBD4-9229 with rheumatoid factor presence, extra-articular involvement or bone erosion in patients with RA. Results suggest that MBD4-8666 and MBD4-9229, but not MBD4-1057, gene polymorphisms are related to RA in Chinese patients in Taiwan.

Thymol-evoked Ca+ mobilization and ion currents in pituitary GH3 cells.

In this study, an attempt was made to elucidate the effects of thymol, a monocyclic phenolic compound, on Ca2+ mobilization and ion currents in pituitary GH3 cells with the aid of fura-2 fluorimetry and the whole-cell voltage-clamp technique. Thymol increased intracellular Ca2+ concentrations ([Ca2+]i) in GH3 cells loaded with Ca2+-sensitive dye fura-2. Removing extracellular Ca2+ reduced the thymol-induced [Ca2+]i rise. In Ca2+ -free solution, thymol-evoked [Ca2+]i rise was unchanged by depleting the Ca2+ store with thapsigargin (1 microM), while the thapsigargin-induced [Ca2+]i rise was reduced by pretreatment with thymol. These results imply that the Ca2+ stores depleted by thymol comprise thapsigargin-sensitive and thapsigargin-insensitive pools. In addition, after depletion of the internal Ca2+ store with 100 microM thymol in Ca2+ -free solution, a subsequent application of Ca2+ greatly induced a [Ca2+]i increase. The results indicate that, similar to thapsigargin, 100 microM thymol may activate the capacitative calcium entry (CCE) channel. However, thymol (100 microM) had a slight depressant action in L-type calcium current (I(CaL)). The stimulatory actions of thymol on Ca2+ signaling may partly be responsible for the underlying cellular mechanisms through which it affects neuroendocrine functions.

Lack of association of interleukin-6 and interleukin-8 gene polymorphisms in Chinese patients with systemic lupus erythematosus.

The purpose of this study was to determine whether interleukin (IL)-6 and IL-8 gene polymorphisms were markers of susceptibility to or severity of systemic lupus erythematosus (SLE) in Chinese patients. The study included 150 Chinese patients with SLE. A total of 130 unrelated healthy individuals living in central Taiwan served as control subjects. Polymorphisms of the IL-6 and IL-8 gene were typed from genomic DNA. The genotypes, allelic frequencies, and carriage rates were compared between SLE patients and control subjects. The relationship between allelic frequencies and clinical manifestations of 135 SLE patients was evaluated. There were no statistically significant differences in IL-6 and IL-8 gene polymorphisms between the SLE and control groups (chi-squared test, P=0.53, chi(2)=1.27 and P=0.44, chi(2)=1.62, respectively). In addition, there was no significant association between the two groups in allelic frequency of IL-6 and IL-8 (P=0.89 and P=0.26, respectively). We also did not detect any association between the IL-6 and IL-8 genotype and clinical or laboratory profiles in SLE patients. The results suggest that the IL-6 and IL-8 gene polymorphisms are not related to SLE.

Effects of 4-piperidinomethyl-2-isopropyl-5-methylphenol on oxidative stress and calcium current.

4-Piperidinomethyl-2-isopropyl-5-methylphenol (THPI) was synthesized by reaction of thymol with piperidine and formaldehyde. The biological effect of THPI on superoxide anion scavenging activity, antiplatelet activity and calcium current inhibition were investigated. THPI (50 microM) was shown to be a scavenger of superoxide radicals in human neutrophils stimulated with N-formyl-Met-Leu-Phe (66% inhibition). Since superoxide anions are essential for platelet aggregation and L-type Ca2+-channel activity, we further found that THPI inhibited platelet aggregation induced by arachidonic acid (IC50 46.80+/-6.88 microM). The effect of THPI on Ca2+ current in NG108-15 cells was investigated using the whole-cell voltage-clamp technique. THPI inhibited voltage-dependent L-type Ca2+ current (ICa, L). The IC50 value of THPI-induced inhibition of ICa, L was 3.60+/-0.81 microM. THPI caused no change in the overall shape of the current-voltage relationship of ICa, L. This indicates that THPI is an inhibitor of ICa, L in NG108-15 cells. Therefore, the channel-blocking properties of THPI may contribute to the underlying mechanism by which it affects neuronal or neuroendocrine function. Furthermore, no significant cytotoxic effects of THPI (0.3-50 microM) were observed in NG108-15 cells. The results indicate that THPI is a potential reactive oxygen species scavenger and may prevent platelet aggregation or inhibit L-type Ca2+-channel activity, possibly by scavenging reactive oxygen species.

No relationship of -627 interleukin-10 promoter polymorphism in Chinese patients with rheumatoid arthritis.

The aim of this study was to examine whether -627 interleukin-10 (IL-10) promoter polymorphism is a marker of susceptibility to or severity of rheumatoid arthritis (RA) in Chinese patients in Taiwan. The study included 198 Chinese patients with RA. One hundred unrelated healthy individuals living in central Taiwan served as the control subjects. The relationship between IL-10 gene polymorphism and clinical manifestations of RA was evaluated. For the genotype, allelic frequency, and carriage rate of IL-10 polymorphism, there were no statistically significant differences found between patients and controls. Furthermore, we did not detect any association of IL-10 genotype with rheumatoid factor (RF), extra-articular involvement, or bone erosion in the RA patients. The lack of association of -627 IL-10 gene polymorphism with RA and the clinical findings in our study implies that the IL-10 gene polymorphism cannot serve as a candidate gene marker for screening RA patients.

Polymorphisms of TAP1 transporter genes in Chinese patients with systemic lupus erythematosus in Taiwan.

The aim of this study was to determine how polymorphisms of transporters associated with transporter and antigen processing 1 (TAP1) alleles contributed to the pathogenesis of systemic lupus erythematosus (SLE) in Taiwan. We collected 88 patients with SLE and 104 healthy people for the control group. The polymorphisms were detected as a result of polymerase chain reaction (PCR)-based restriction analysis. Associations between SLE and TAP1 polymorphisms were evaluated. The results revealed no significant differences between the healthy individuals and SLE patients with TAP1-1 (Dpn II) and TAP1-2 (Acc I) polymorphisms ( P=0.10 and 0.36, respectively). However, the G alleles of TAP1-1 and TAP1-2 were significantly more common than the A alleles in serositis of SLE patients (chi(2)=11.16 and P=0.004, chi(2)=8.10 and P=0.02, respectively).