Recent Progress Made In Our Genetic Study
Analysis of lupus patients and their families is particularly helpful in the pursuit of the SLE susceptibility genes. Using the families that have participated in our study, our team has identified a region on human chromosome 1 that is linked to the predisposition for the development of SLE in certain individuals. The chromosomes are structures that consist of highly packed DNA, the molecule that carries the genetic information (or genes). We have concentrated our efforts on the analysis of this particular segment of DNA in SLE affected individuals and their family members. We are currently working on fine mapping, or taking a closer look at this small region of chromosome 1 in order to pinpoint a possible lupus susceptibility gene.
In families with a lupus sibpair, two siblings have the disease, we have also examined their individual disease manifestations. We observed, that genetically related individuals, brothers and sisters, compared to unrelated individuals are more likely to share similar SLE manifestations such as: low platelet counts, skin rash, neurological symptoms, and anemia, suggesting that these traits might run in families.
So far, we have enrolled more than 500 SLE families in our project, but to narrow this particular chromosomal region, and other potential regions, for the identification of a genetic risk factor, we need to analyze even larger numbers of SLE families.This is why your participation in our study is so helpful to us. Every new family teaches us something new about the disease and gives us new insight into the genetic factors that may contribute to the development of lupus
Publications From Our Study
1. Tsao BP, Cantor RM, Kalunian KC, Chen C-J, Badsha H, Singh R, Wallace DJ, Kitridou RC, Chen S-L, Shen N, Song YW, Isenberg DA, Yu C-L, Hahn BH, Rotter JI. Evidence for linkage of a candidate chromosome 1 region to human SLE. J. Clin. Invest., 99:725-731, 1997.
2. Tsao BP. “Genetic susceptibility to lupus nephritis.” Lupus. 7:585-590, 1998.
3. Song YW, Han C-W, Kang S-W, Baek H-J, Lee E-B, Shin C-H, Hahn BH, Tsao BP. Abnormal distribution of FcgRlla polymorphism in patients with SLE. Arthritis Rheum, 41:421-426, 1998.
4. Tsao BP, Cantor RM, Grossman JM, Shen N, Teophilov NT, Wallace DJ, Arnett FC, Hartung K, Goldstein R, Kalunian KC, Hahn BH, Rotter JI. PARP alleles within the linked chromosomal region are associated with SLE. J. Clin. Invest., 103:1135-1140, 1999.
5. Wu J, Edberg JC, Gibson AW, Tsao BP, Kimberly RP. Single nucleotide polymorphisms of TCR z-chain of SLE patients. Arthritis Rheum, 42:2593-2600, 1999.
6. Tsao BP. “Lupus susceptibility genes on human chromosome 1.” Int. Rev. Immunol.19:319-334,2000.
7. Tsao BP, Cantor R M, Grossman JM, Shen N, Teophilov NT, Wallace DJ, Arnett FC, Hartung K, Goldstein R, Kalunian KC, Hahn BH, Rotter JI. PARP alleles and susceptibility to SLE. J. Clin. Invest. (letter), 105:1501-1502, 2000.
8. Boorboor P, Drescher BE, Hartung K, Sachse C, Tsao BP, Schneider PM, Kalden JR, Lakomek HJ, Peter HH, Schmidt RE, Witte T. Poly (ADP-ribose) polymerase polymorphisms are not a genetic risk factor for SLE in German Caucasians. J. Rheumatol. (letter) 27:2061, 2000.
9. Grossman JM, Tsao BP. Genetics and SLE. Current Rheumatology Reports, 2:13-18, 2000.
10. Tan FK, Reveille JD, Arnett FC, Stivers DN, Tsao BP. Poly (ADP-Ribose) polymerase alleles in African American SLE patients. Arthritis Rheum., 43:1421-1422, 2000 (letter).
11. Tsuchiya N, Kawasaki A, Tsao BP, Komata T, Grossman GM, Tokunaga K. “Analysis on the association of HLA-DRB1 and TNFA promoter polymorphisms with SLE using transmission disequilibrium test.” Genes and Immunity, 2: 317-322, 2001.
12. Lee EB, Lee YJ, Baek HJ, Kang SW, Chung ES, Shin CH, Hong KM, Kim HA, Tsao BP, Hahn BH, Song YW. “Fc gamma receptor IIIA polymorphism in Korean patients with systemic lupus erythematosus: association with anti-dsDNA antibody.” Rheum International, 21:222-226, 2002.
13. Tsao BP and Hahn BH. The genetics of systemic lupus erythematosus. In Emery and Rimoin’s Principles and practice of Medical Genetics, 4th Edition. UK: Harcourt Publishers Limited. Pg 2012-2027, 2002.
14. Tsao BP. “The Genetics of Human SLE.” In: DJ Wallace and BH Hahn, eds. Dubois’ Lupus Erythematosus, 6th Edition, Philadelphia: Lippincott, Williams & Wilkins. Pg 97-120, 2002.
15. Tsao BP. An Update on Genetic Studies of SLE Current Rheumatology Reports. 4:359-67, 2002.
16. Kuroki K, Tsuchiya N, Tsao BP, Grossman JM, Fukazawa T, Hagiwara K, Kano H, Takazoe M, Iwata T, Hashimoto H, Tokunaga K. Association of CD19 Polymorphisms with Susceptibility to SLE in Japanese. Genes and Immunity, Suppl 1:S21-30, 2002.
17. Tsao BP, Cantor RM, Grossman JM, Kim SK, Lau CS, Chen C-J, Shen N, Ginzler EM, Goldstein R, Kalunian KC, Arnett FC, Wallace DJ, Hahn BH “Linkage and Interaction of Loci at 1q23 and 16q12 may contribute to susceptibility to systemic lupus erythematosus.” Arthritis & Rheum. 46: 2928-2936,2002.
18. Tsao BP, Grossman JM, Riemekasten G, Strong N, Kalsi J, Wallace DJ, Chen C-J, Lau CS, Ginzler EM, Goldstein R, Kalunian KC, Harley JB, Arnett FC, Hahn BH, Cantor RM. “Familiality and co-occurrence of clinical features of systemic lupus erythematosus.” Arthritis & Rheum. 46:2678-2685,2002.