K W Lee

Queen Mary Hospital, Hong Kong, Hong Kong

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Publications (8)23.85 Total impact

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    ABSTRACT: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohn's disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established. In this study, using a collection of 612 SLE patients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls. The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10(-7); rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production. A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.
    Full-text · Article · Jan 2012 · Lupus
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    ABSTRACT: UHRF1BP1 encodes a highly conserved protein with unknown function. Previously, a coding variant in this gene was found to be associated with systemic lupus erythematosus (SLE) in populations of European ancestry (rs11755393, R454Q, P=2.22 x 10⁻⁸, odds ratio=1.17). In this study, by a combination of genome-wide study and replication involving a total of 1230 patients and 3144 controls, we confirmed the association of this coding variant to SLE in Hong Kong Chinese. We also identified another coding variant in this gene that independently contributes to SLE susceptibility (rs13205210, M1098T, P=4.44 x 10⁻⁹, odds ratio=1.49). Cross-population confirmation establishes the involvement of this locus in SLE and indicates that distinct alleles are contributing to disease susceptibility.
    No preview · Article · Feb 2011 · Genes and immunity
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    ABSTRACT: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Recently, single nucleotide polymorphisms (SNPs) in BANK1 and TNFSF4 have been shown to be associated with SLE in Caucasian populations, but it is not known whether they are also involved in the disease in other ethnic groups. Recent data from our genome-wide association study (GWAS) for 314 SLE cases and 920 controls collected in Hong Kong identified SNPs in and around BANK1 and TNFSF4 to be associated with SLE risk. On the basis of the results of the reported studies and our GWAS, SNPs were selected for further genotyping in 949 SLE patients (overlapping with the 314 cases in our GWAS) and non-overlapping 1042 healthy controls. We confirmed the associations of BANK1 and TNFSF4 with SLE in Chinese (BANK1, rs3733197, odds ratio (OR)=0.84, P=0.021; BANK1, rs17266594, OR=0.61, P=4.67 x 10(-9); TNFSF4, rs844648, OR=1.22, P=2.47 x 10(-3); TNFSF4, rs2205960, OR=1.30, P=2.41 x 10(-4)). Another SNP located in intron 1 of BANK1, rs4522865, was separately replicated by Sequenom in 360 cases and 360 controls and was also confirmed to be associated with SLE (OR=0.725, P=2.93 x 10(-3)). Logistic regression analysis showed that rs3733197 (A383T in ankyrin domain) and rs17266594 (a branch point-site SNP) from BANK1 had independent contributions towards the disease association (P=0.037 and 6.63 x 10(-8), respectively). In TNFSF4, rs2205960 was associated with SLE independently from the effect of rs844648 (P=6.26 x 10(-3)), but not vice versa (P=0.55). These findings suggest that multiple independent genetic variants may be present within the gene locus, which exert their effects on SLE pathogenesis through different mechanisms.
    Full-text · Article · May 2009 · Genes and immunity
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    ABSTRACT: In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific.
    Full-text · Article · Mar 2009 · Genes and immunity
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    C.C. Mok · K.W. Lee · C.T.K. Ho · C.S. Lau · R.W.S. Wong
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    ABSTRACT: To study the survival rate and prognostic indicators of systemic lupus erythematosus (SLE) in a southern Chinese population. One hundred and eighty-six patients with SLE diagnosed between 1992 and 1999 were prospectively followed. Clinical features at presentation, subsequent evolving features, autoantibody profile, damage scores and mortality data were obtained. Prognostic factors for survival were studied by statistical analysis. One hundred and sixty-three female and 23 male SLE patients were studied. The female to male ratio was 7.1 to 1 and the mean age at presentation was 33.6 yr (range 12-75). The mean disease duration was 45.2 months. At diagnosis, arthritis, malar rash and alopecia were the commonest features. During follow-up, the prevalence of nephritis, arthritis, photosensitivity and haematological disease increased significantly. Thirty-one per cent of the patients had organ damage at the time of data analysis and renal disease was the commonest cause. Logistic regression revealed that central nervous system disease, discoid lesions and treatment with high-dose steroid were independent predictors for damage. Nine patients died during the study period (three of disease-related complications and six of infections). The 3-, 5-, and 7-yr survival rates of our cohort were 97, 93 and 93%, respectively. Cox regression analysis revealed that thrombocytopenia and high-dose steroid treatment were independent risk factors for mortality. The survival of SLE in our southern Chinese patients is similar to that of the Caucasian series reported in the 1990s. Although nephritis contributes to organ damage, it is not a major determinant for survival. Infection remains the commonest cause of death. High-dose steroid treatment and thrombocytopenia are independent risk factors for mortality. Judicious use of immunosuppressive agents is necessary to improve the short-term survival of SLE.
    Full-text · Article · May 2000 · Rheumatology
  • C C Mok · C S Lau · K W Lee · R. W. S. Wong
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    ABSTRACT: To study prospectively the serum prolactin (PRL) concentrations among male patients with systemic lupus erythematosus (SLE) and their possible relationship to disease activity and manifestations. Serum PRL levels were measured by radioimmunoassay in 31 male patients with SLE and 31 age matched controls. Demographic, clinical, and laboratory features of the patients were obtained. Mean PRL levels from both groups were compared, and PRL from patients with SLE was correlated with variables of disease activity, including the SLE Disease Activity Index (SLEDAI), complement level, and anti-dsDNA titer. Thirteen patients were followed serially and changes in PRL levels in relation to fluctuation in disease activity were evaluated. Mean PRL levels were higher in male patients with SLE than healthy controls; however, the difference did not reach statistical significance (230 vs 194 mIU/l; p = 0.06). Hyperprolactinemia was found in 4 patients (13%) and was not associated with particular clinical manifestations or autoantibodies. Considering all patients as a whole, PRL levels did not correlate with variables of disease activity and there was no difference in PRL between patients with active versus inactive disease. A subanalysis of the 4 hyperprolactinemic patients revealed a higher SLEDAI score than those with normal PRL (8.8 vs 3.7; p = 0.20); however, the difference was not statistically significant. Among the hyperprolactinemic patients, PRL levels did not correlate with SLEDAI score or anti-dsDNA titer. Prospective studies of PRL levels in 13 patients did not indicate a role of PRL in the monitoring of disease activity or predicting relapses. Hyperprolactinemia occurred in a small proportion of male patients with SLE and its significance remained unclear. Serum PRL level did not correlate with disease activity and was not a reliable marker for disease monitoring.
    No preview · Article · Jan 1999 · The Journal of Rheumatology
  • C C Mok · K W Lee · R.W.S. Wong · C S Lau

    No preview · Article · Jan 1999 · Clinical and experimental rheumatology
  • C C Mok · C S Lau · C T Ho · K W Lee · M Y Mok · R W Wong
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    ABSTRACT: It remains controversial whether administration of exogenous estrogens is safe in systemic lupus erythematosus (SLE). The current study was undertaken to determine the effect of hormone replacement therapy (HRT) on the rate and magnitude of flares in a cohort of postmenopausal SLE patients. Thirty-four patients were prospectively followed. The frequency and severity of disease exacerbations in 11 patients who received HRT was compared with 23 patients who did not receive HRT. Our results showed that both users and non-users of HRT had a comparable age of disease onset, duration of disease, clinical manifestations, and duration of follow-up. No significant increase in the rate (0.12 relapses/patient-year in HRT group vs 0.16 relapses/patient-year in the non-HRT group, p = 0.90) or magnitude (total SLEDAI score increase during flares/patient-year in the HRT and non-HRT groups were 0.55 and 1.22, respectively, p = 0.57) of flares could be demonstrated in patients who received HRT over a median follow-up period of 35 months. We concluded that HRT appeared to be well tolerated and safe in postmenopausal SLE patients. Its potential beneficial effect may outweigh its deleterious effect on disease activity.
    No preview · Article · Feb 1998 · Scandinavian Journal of Rheumatology