CYP2D6 genetic polymorphisms in Saudi systemic lupus erythematosus patients: A cross-sectional study.

To determine the prevalence of selected single nucleotide polymorphisms (rs1080985, rs28624811, rs1065852, rs28371725, and rs1135840) in cytochrome P450 2D6 (CYP2D6) gene among Saudi systemic lupus erythematosus (SLE) patients and to investigate the association between the genetic variants and clinical features of SLE. This cross-sectional study was carried out on adult Saudi patients at King Khalid University Hospital, Riyadh, Saudi Arabia. Patients with confirmed SLE based on the 2012 Systemic Lupus International Collaborating Clinics classification criteria were included in the study. Peripheral blood was collected for genomic deoxyribonucleic acid extraction and TaqMan® technologies were used for target genotyping. For statistical analysis, differences in genotype frequencies were determined using the Chi-square test, and the association between the variant genotypes and SLE features was evaluated using logistical regression models. There were 107 participants included in this study. Overall, the most predominant (23.4%) recessive genotype was AA in rs28624811, and the least prevalent (1.9%) recessive genotype was TT in rs28371725. Moreover, the variant rs1080985 genotypes (GC or CC) were significantly associated with the presence of serositis manifestation (OR=3.15, p=0.03), even after adjusting for age and gender. However, the dominant rs28624811 genotype (GG) was associated with renal involvement (OR=2.56, p=0.03). Systemic lupus erythematosus patients carrying CYP2D6 variants might be considered at risk for certain manifestations of SLE. Further studies are needed to investigate the implication of these genetic variations in clinical outcomes and drug response.

Hassen LM ，Daghestani MH ，Omair MA ，Althomali AK ，Almukaynizi FB ，Almaghlouth IA ... -  《-》

Genetic susceptibility and clinical features of CYP2D6 associated with systemic lupus erythematosus in a Chinese population.

Luo X ，Du J ，Zhao J ，Fan M ，Luo X ，Zhao P ，Zheng P ，Mo L ，Li Y ... -  《-》

Association of Polymorphisms of Cytochrome P450 2D6 With Blood Hydroxychloroquine Levels in Patients With Systemic Lupus Erythematosus.

To evaluate associations of genetic polymorphisms in cytochrome P450 (CYP) isoforms 2D6, 3A5, and 3A4 with blood concentrations of hydroxychloroquine (HCQ) and its metabolite, N-desethyl HCQ (DHCQ), in patients with systemic lupus erythematosus (SLE). SLE patients taking HCQ for >3 months were recruited and were genotyped for 4 single-nucleotide polymorphisms in CYP2D6*10, CYP3A5*3, and CYP3A4*18B. Blood HCQ and DHCQ concentrations ([HCQ] and [DHCQ]) were measured and their association with corresponding genotypes was investigated. A total of 194 patients were included in the analysis. CYP2D6*10 polymorphisms (rs1065852 and rs1135840) were significantly associated with the [DHCQ]:[HCQ] ratio after adjustment for age, sex, dose per weight per day, and SLE Disease Activity Index score (P = 0.03 and P < 0.01, respectively). In adjusted models, the [DHCQ]:[HCQ] ratio was highest in patients with the G/G genotype of the CYP2D6*10 (rs1065852) polymorphism and lowest in those with the A/A genotype (P = 0.03). Similarly, the [DHCQ]:[HCQ] ratio was highest in patients with the C/C genotype of the CYP2D6*10 (rs1135840) polymorphism and lowest in those with the G/G genotype (P < 0.01). The CYP2D6*10 (rs1065852) polymorphism was significantly related to the [DHCQ] (P = 0.01). However, the polymorphisms of CYP3A5*3 and CYP3A4*18B did not show any significant association with the [HCQ], [DHCQ], or [DHCQ]:[HCQ] ratio. Our study showed that the [DHCQ]:[HCQ] ratio was related to CYP2D6 polymorphisms in Korean lupus patients taking oral HCQ. CYP polymorphisms may explain why there is wide variation in blood HCQ concentrations. The role of an individual's CYP polymorphisms should be considered when prescribing oral HCQ.

Lee JY ，Vinayagamoorthy N ，Han K ，Kwok SK ，Ju JH ，Park KS ，Jung SH ，Park SW ，Chung YJ ，Park SH ... -  《-》

ICOS gene polymorphisms in systemic lupus erythematosus: A case-control study.

The inducible T-cell costimulator (ICOS) may play an important role in adaptive immunity by regulating the interaction between T cells and antigen-presenting cells. Disruption of this molecule can lead to autoimmune diseases, in particular systemic lupus erythematosus (SLE). In this study, we aimed to explore the possible association between ICOS gene polymorphisms and SLE as well as their influence on disease susceptibility and clinical outcomes. A further objective was to assess the potential impact of these polymorphisms on RNA expression. A case-control study, including 151 patients with SLE, and 291 unrelated healthy controls (HC) matched in gender, and geographical origin, was performed to genotype two polymorphisms located in the ICOS gene: rs11889031 (-693 G/A) and rs10932029 (IVS1 + 173 T/C); using the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The different genotypes were validated by direct sequencing. The expression level of ICOS mRNA was assessed by quantitative PCR in peripheral blood mononuclear cells of SLE patients and HC. The results were analysed using Shesis and spss.20. Our results revealed a significant association between ICOS gene rs11889031 > CC genotype and SLE disease (codominant genetic model 1, (C/C vs. C/T), p = .001, odds ratio [OR] = 2.18 IC [1.36-3.49]); codominant genetic model 2, (C/C vs. T/T) p = .007, OR = 15.29 IC [1.97-118.5]); dominant genetic model, (C/C vs. C/T + T/T) p = .0001, OR = 2.44 IC [1.53-3.9]). Besides, there was a marginal association between rs11889031 > TT genotype and T allele with a protective role from SLE (recessive genetic model, p = .016, OR = 0.08 IC [0.01-0.63] and p = 7.6904E - 05, OR = 0.43 IC = [0.28-0.66], respectively). Moreover, statistical analysis indicated that the rs11889031 > CC genotype was linked with clinical and serological manifestations of SLE, including blood pressure, and anti-SSA antibodies production in SLE patients. However, the ICOS gene rs10932029 polymorphism was not associated with susceptibility to SLE. On the other side, we did not note any effect of the two selected polymorphisms on the level of ICOS mRNA gene expression. The study showed a significant predisposing association of the ICOS rs11889031 > CC genotype with SLE, in contrast to a protective effect of rs11889031 > TT genotype in Tunisian patients. Our results suggest that ICOS rs11889031 may act as a risk factor for SLE and could be used as a genetic susceptibility biomarker.

Houssaini H ，Bouallegui E ，Abida O ，Tahri S ，Elloumi N ，Hachicha H ，Marzouk S ，Bahloul Z ，Masmoudi H ，Fakhfakh R ... -  《-》

Association of omentin-1, adiponectin, and resistin genetic polymorphisms with systemic lupus erythematosus in a Chinese population.

An increasing number of studies have demonstrated the roles of adipokines in systemic lupus erythematosus (SLE). We aimed to investigate the association of genetic variations of omentin-1, adiponectin, and resistin with SLE susceptibility. We selected 623 SLE patients and 665 normal controls in the present study. Genotyping of omentin-1 rs2274907, rs35779394, rs79209815, and rs13376023; adiponectin rs16861194 and rs266729; and resistin rs1862513, rs3745368, and rs3745367 was conducted by TaqMan SNP genotyping assays. Overall, we found no significant differences in the allele or genotype frequencies of the nine studied SNPs between the SLE patients and controls. However, an increased frequency of the resistin rs3745368 variant was observed in the SLE patients under the dominant model (P = 0.024). In omentin-1, the rs13376023 A allele was found to be related to oral ulcers in SLE patients (P = 0.013), and the rs35779394 C and rs13376023 A allele frequencies were significantly lower in SLE patients with BMI ≥ 24 kg/m2 (P = 0.019, P = 0.033, respectively). For resistin, the frequencies of the rs3745368 AA genotype and A allele were lower in SLE patients with discoid rash (P = 0.036, P = 0.011), and the rs3745368 A allele frequency was higher in SLE patients with lupus nephritis (P = 0.018). The resistin rs3745367 AA genotype and A allele frequencies were related to the occurrence of renal disorder in SLE patients (P = 0.024, P = 0.009). The haplotype analysis showed that the CGA haplotype of resistin was associated with susceptibility to SLE (P = 0.005). No significant associations of plasma omentin-1, adiponectin or resistin levels with their respective genotypes were found in SLE patients. In summary, omentin-1, adiponectin and resistin SNPs are not associated with the genetic background of SLE in Chinese patients. However, omentin-1 and resistin genetic variations might contribute to several clinical phenotypes of SLE.

Zhang TP ，Li HM ，Li R ，Zhang Q ，Fan YG ，Li XM ，Pan HF ，Ye DQ ... -  《-》