Department Introduction
Excellence
Systemic lupus erythematosus (SLE) is a rheumatic disease in which the body’s immune system mistakenly attacks healthy tissue in many parts of the body and causes chronic inflammation. SLE is more prevalent in women, but it also common in men, children and the elderly.
SLE is an autoimmune disease of unknown aetiology. According to latest medical research, it is generally accepted that human leukocyte antigen (HLA) and complement component deficiency are associated with SLE. According to an epidemiologic research from Hawaii, some specific races tend to have higher prevalence of SLE. For example, the prevalences of SLE in Chinese, Japanese and Filipino are four times higher than that in Caucasian. The genetic research also found that people with SLE serum have family members with higher motbidity of SLE.
A single-nucleotide polymorphism (SNP) determines the differences between members of a biological species or paired chromosomes in a human; thereby, scientists can find disease susceptibility genes in individuals and make personalized medicine possible. From an evolutionary point of view, single nucleotide polymorphisms (SNPs) are stable. SNPs are also being used in studies of human evolution since that the variation in SNPs is unnoticeable throughout generations.
A SNP marker found in coding regions leads to the change of structure and function of protein which makes people tend to have certain diseases or change their reaction to certain drugs. A SNP marker found in non-coding regions lead to different gene expressions.
By genetic susceptibility analysis, we can make sure which ethnic groups are more likely to have certain diseases and provide them early intervention in terms of the diet and lifestyle. Those researches will bring huge contributions to disease prevention. In addition, by the research of SNP in drug metabolism, the differences of drug metabolism and efficacy among patients can be explained and the different medications and doses can be implemented in accordance with individuals' genetic background.
We conducts a series of SNP researches which strongly indicate that the morbidity of autoimmune diseases and the clinical symptoms are related to the genetic polymorphisms (CD4, IL-2, IL-18, IL-10 and TNF-gamma)
Lupus nephritis (LN) is a major determinant of morbidity and mortality in SLE since more than 50% of patients will develop nephritis. Many researches show that lupus nephritis is believed to be related to excessive T cell immune response. Interleukin 18 (IL-18) is a cytokine belonging to Type 1 T helper cells.
Our researches suggest that genetic polymorphisms -137 and -607 in the IL-18 promoter are involved in the development of LN. Haplotypes -607A/-137G seems to be associated with protective effect against development of LN.
Previous researches have shown that, in Caucasian patients with SLE, one haplotype (GCC: -1082G/-819C/-592C) in the IL-10 gene is associated with the invasion of the kidney disease. Moreover, IL-10 -592 C allele is associated with the low risk of SLE. However, in Chinese patients, another haplotype (ATA: -1087A/-824T /-597A) in the IL-10 gene is associated with the invasion of the kidney disease as well.
DNA damage is related to the cancer incidence rate. The DNA repair mechanisms are to repair the base deletion, the mechanism of preventing mutation. When mutations happen to DNA damage repair genes, DNA repair system cannot repair damaged DNA and lead to the development of cancers.
Our researches reveal that genetic variant of XRCC1 is related to the morbidity of SLE. XRCC1 (X-ray repair cross complementing group 1) is involved in the base deletion repair and translates to the scaffolding protein which participates in the repair of DNA single-strand breaks. XRCC1 has eight different SNPs. Three polymorphisms of the XRCC1 gene at codons 194, 280 and 399 leading to amino acid changes are found to alter the efficiency of the DNA repair system and may therefore constitute potential cancer risk.
We have researches on genetic polymorphism in rheumatic disorders caused by other chronic autoimmune dysfunction as well.