Biomedical subjects

F K Tan

Publications and source records attributed to F K Tan.

22 records · Page 2Linked to original sources

PubMed1999

Autoantibodies to the extracellular matrix microfibrillar protein, fibrillin 1, in patients with localized scleroderma.

OBJECTIVE: Serum autoantibodies to fibrillin 1, the major component of microfibrils in the extracellular matrix, recently have been reported to occur in the tight skin mouse and in patients with systemic sclerosis, but not in patients with other connective tissue diseases. This study was undertaken to determine whether antifibrillin 1 antibodies could be detected in patients with localized forms of scleroderma. METHODS: Sera from 50 patients with localized scleroderma (27 with linear scleroderma and 23 with morphea) and 51 normal controls were tested for IgG and IgM antifibrillin 1 autoantibodies, using a radioimmunoassay (RIA) and a human recombinant fibrillin 1 protein (rFbn-1). RESULTS: Both in patients with linear scleroderma and in those with morphea, mean levels of IgM and IgG binding to rFbn-1 were significantly higher than in controls. Eight patients with linear scleroderma (30%) and 6 patients with morphea (26%) had IgG autoantibodies to fibrillin 1 (rFbn-1) by RIA, compared with 3 controls (6%) (P = 0.006 and P = 0.022, respectively). No correlations between antifibrillin 1 antibodies and active skin disease or antinuclear antibody positivity were found. CONCLUSION: Autoantibodies to fibrillin 1 occur in patients with both forms of localized scleroderma (linear scleroderma and morphea). The clinical and pathogenetic significance of this autoimmune response remains to be determined.

Autoantibodies↗

PubMed1999

HLA haplotypes and microsatellite polymorphisms in and around the major histocompatibility complex region in a Native American population with a high prevalence of scleroderma (systemic sclerosis).

Choctaw Native Americans in southeastern Oklahoma have the highest prevalence of scleroderma or systemic sclerosis yet found (469/100,000). An Amerindian HLA DR2 haplotype (DRB1*1602) was significantly associated with scleroderma in this population in a previous study. It is not known, however, if other disease genes are linked to this HLA haplotype. The regions flanking the HLA loci were studied with polymorphic microsatellite markers. An extended HLA DR2 (DRB1*1602, DQA1*0501, DQB1*0301, DPB1*1301) haplotype that includes the class I and III regions was identified which was significantly associated with scleroderma in the Oklahoma Choctaw. No other significant associations with microsatellite marker alleles immediately flanking the HLA region were found.

Autoimmune Diseases↗

PubMed1998

Association of microsatellite markers near the fibrillin 1 gene on human chromosome 15q with scleroderma in a Native American population.

OBJECTIVE: To localize disease genes for scleroderma, or systemic sclerosis (SSc), in a population of Choctaw Native Americans with a high prevalence of SSc, in which there is evidence of a possible founder effect. METHODS: A candidate gene approach was used in which microsatellite alleles on human chromosomes 15q and 2q, homologous to the murine tight skin 1 (tsk1) and tsk2 loci, respectively, were analyzed in Choctaw SSc cases and race-matched normal controls for possible disease association. Genotyping first-degree relatives of the cases identified potential disease haplotypes, and haplotype frequencies were obtained by expectation-maximization and maximum-likelihood estimation methods. Simultaneously, the ancestral origins of contemporary Choctaw SSc cases were ascertained using census and historical records. RESULTS: A multilocus 2-cM haplotype was identified on human chromosome 15q homologous to the murine tsk1 region, which showed a significantly increased frequency in SSc cases compared with controls. This haplotype contains 2 intragenic markers for the fibrillin 1 (FBN1) gene. Genealogical studies demonstrated that the SSc cases were distantly related, and their ancestry could be traced back to 5 founding families in the mid-eighteenth century. The probability that the SSc cases share this haplotype due to familial aggregation effects alone was calculated and found to be very low. There was no evidence of any microsatellite allele disturbances on chromosome 2q in the region homologous to the tsk2 locus or the region containing the interleukin-1 family. CONCLUSION: A 2-cM haplotype on chromosome 15q that contains FBN1 is associated with scleroderma in Choctaw Native Americans from Oklahoma. This haplotype may have been inherited from common founders about 10 generations ago and may contribute to the high prevalence of SSc that is now seen.

Alleles↗

PubMed1998

The genetics of lupus.

Genetic factors strongly influence the risk for systemic lupus erythematosus (SLE). Studies in both animal models and humans suggest that SLE is a complex trait with contributions from multiple genes. Recent genetic studies have shown that polymorphisms at several loci, including the major histocompatibility complex, complement proteins, immunoglobulin receptors, cytokines, and other as yet unmapped genes, are associated with SLE. Ethnic factors are also important because some of these genetic associations are only found in certain populations. Murine models of SLE have provided rational candidate loci to begin genome-wide studies in humans. Promising results are now emerging from such studies.

Animals↗