Interindividual gene copy-number variation (CNV) of complement component C4 and its associated po... more Interindividual gene copy-number variation (CNV) of complement component C4 and its associated polymorphisms in gene size (long and short) and protein isotypes (C4A and C4B) probably lead to different susceptibilities to autoimmune disease. We investigated the C4 gene CNV in 1,241 European Americans, including patients with systemic lupus erythematosus (SLE), their first-degree relatives, and unrelated healthy subjects, by definitive genotyping and phenotyping techniques. The gene copy number (GCN) varied from 2 to 6 for total C4, from 0 to 5 for C4A, and from 0 to 4 for C4B. Four copies of total C4, two copies of C4A, and two copies of C4B were the most common GCN counts, but each constituted only between one-half and three-quarters of the study populations. Long C4 genes were strongly correlated with C4A (R=0.695; P<.0001). Short C4 genes were correlated with C4B (R=0.437; P<.0001). In comparison with healthy subjects, patients with SLE clearly had the GCN of total C4 and C4...
.................................................................................................... more .............................................................................................................. ii Dedication ........................................................................................................... v Acknowledgments ............................................................................................. vi Vita ...................................................................................................................... ix List of Tables .................................................................................................... xv List of Figures ................................................................................................. xvii Abbreviations and symbols ......................................................................... xviix Chapter
Background Antiphospholoipid syndrome (APS) is the association of antiphospholipid antibodies (aP... more Background Antiphospholoipid syndrome (APS) is the association of antiphospholipid antibodies (aPL) with thromboses and/or recurrent pregnancy loss (RPL). Among patients with SLE, one-third have aPL and 10%–15% have a manifestation of secondary APS. Although mouse models suggested complement drives the pathogenesis of APS, we have little knowledge on how complement proteins and genes contribute to the pathology of human APS, and the concurrence of SLE and APS. Methods We performed a cross-sectional study on complement proteins and genes in 525 patients with aPL. Among them, 237 experienced thromboses and 293 had SLE; 111 had both SLE and thromboses, and 106 had neither SLE nor thrombosis. Complement protein levels were determined by radial immunodiffusion for C4, C3 and factor H; and by functional ELISA for mannan binding lectin (MBL). Total C4, C4A and C4B gene copy numbers (GCN) were measured by TaqMan-based realtime PCR. Results Two to six copies of C4 genes are frequently presen...
Inter-individual gene copy-number variations (CNVs) probably afford human populations the flexibi... more Inter-individual gene copy-number variations (CNVs) probably afford human populations the flexibility to respond to a variety of environmental challenges, but also lead to differential disease predispositions. We investigated gene CNVs for complement ...
Interindividual gene copy-number variation (CNV) of complement component C4 and its associated po... more Interindividual gene copy-number variation (CNV) of complement component C4 and its associated polymorphisms in gene size (long and short) and protein isotypes (C4A and C4B) probably lead to different susceptibilities to autoimmune disease. We investigated the C4 gene CNV in 1,241 European Americans, including patients with systemic lupus erythematosus (SLE), their first-degree relatives, and unrelated healthy subjects, by definitive genotyping and phenotyping techniques. The gene copy number (GCN) varied from 2 to 6 for total C4, from 0 to 5 for C4A, and from 0 to 4 for C4B. Four copies of total C4, two copies of C4A, and two copies of C4B were the most common GCN counts, but each constituted only between one-half and three-quarters of the study populations. Long C4 genes were strongly correlated with C4A (R=0.695; P<.0001). Short C4 genes were correlated with C4B (R=0.437; P<.0001). In comparison with healthy subjects, patients with SLE clearly had the GCN of total C4 and C4...
.................................................................................................... more .............................................................................................................. ii Dedication ........................................................................................................... v Acknowledgments ............................................................................................. vi Vita ...................................................................................................................... ix List of Tables .................................................................................................... xv List of Figures ................................................................................................. xvii Abbreviations and symbols ......................................................................... xviix Chapter
Background Antiphospholoipid syndrome (APS) is the association of antiphospholipid antibodies (aP... more Background Antiphospholoipid syndrome (APS) is the association of antiphospholipid antibodies (aPL) with thromboses and/or recurrent pregnancy loss (RPL). Among patients with SLE, one-third have aPL and 10%–15% have a manifestation of secondary APS. Although mouse models suggested complement drives the pathogenesis of APS, we have little knowledge on how complement proteins and genes contribute to the pathology of human APS, and the concurrence of SLE and APS. Methods We performed a cross-sectional study on complement proteins and genes in 525 patients with aPL. Among them, 237 experienced thromboses and 293 had SLE; 111 had both SLE and thromboses, and 106 had neither SLE nor thrombosis. Complement protein levels were determined by radial immunodiffusion for C4, C3 and factor H; and by functional ELISA for mannan binding lectin (MBL). Total C4, C4A and C4B gene copy numbers (GCN) were measured by TaqMan-based realtime PCR. Results Two to six copies of C4 genes are frequently presen...
Inter-individual gene copy-number variations (CNVs) probably afford human populations the flexibi... more Inter-individual gene copy-number variations (CNVs) probably afford human populations the flexibility to respond to a variety of environmental challenges, but also lead to differential disease predispositions. We investigated gene CNVs for complement ...
Uploads