Osteoarthrosis of the knee (OA), also known as degenerative arthritis of the knee, is a common chronic arthritis, mostly seen in the elderly. Epidemiological surveys show a prevalence of 40% in people aged 55-64 years, and its incidence is increasing every year as the world’s aging population increases. With the rapid progress of gene research, it presents us with a wide research space for osteoarthritis to find its related genes as soon as possible, so as to provide a theoretical basis for gene therapy. Epidemiological studies have shown that OA has a strong genetic predisposition, and some previous studies have identified and confirmed the existence of OA-related susceptibility genes. It is also believed that the pathogenesis of OA is more inclined to the role of complex polygenic regulation. The genes that may be involved include: 1, estrogen receptor gene polymorphism human estrogen receptor d gene is located on chromosome 6, q24-q27, a total of more than 140,000 base pairs, including eight exons and seven introns. The most common polymorphisms within the estrogen receptor d gene are the B polymorphism (BstU I enzyme cut site) located in exon 1, a nonsense mutation, i.e., codon 87 GCG —,GCC (both alanine); the Puv II enzyme cut site located in the first intron, a one-point mutation (T- C) approximately 4o0 bp upstream of the second exon. The XbaI enzyme cut site is located approximately 5O bp downstream of the Puv II enzyme cut site, also within the first intron, and is a one-point mutation. Current studies on estrogen receptor d gene polymorphisms associated with the onset or various symptoms of osteoarthritis have focused on the study of Puv II and Xba I restriction fragment length polymorphisms and Puv II, Xba I and Btg I single nucleotide polymorphisms within their genes. Bergink et al. studied 1483 Rotterdamans aged >55 years and found 54% of px genotypes, 34% of PX genotypes, 12% of PX genotypes, and O% of px genotypes. And the Px allele was strongly associated with radiographic osteoarthritis (radiographic OA, radiographic osteoarthritis of the knee). The OR for radiographic osteoarthritis of the knee was 1.3 (95% CI) for heterozygotes and 2.2 (95% CI) for heterozygotes. Similar results were obtained if statistical analysis was based on gender factors. That is, the PX allele is a risk genotype for radiographic osteoarthritis of the knee. In 1998, Ushiyama et al. studied the restriction fragment length polymorphisms of Puv II and Xba I within the ‘estrogen receptor gene in 318 healthy women and 65 patients with osteoarthritis in Japan, and found that the frequency of the PpXx genotype was significantly higher in patients with osteoarthritis than in controls, (DR = 1. 86, 95% CI = 1.03 to 3.24; JP: 0.039) concluded that the PpXx genotype is a genetic marker for osteoarthritis. 2. collagen Type II pre-collagen (COL2A1) Palotie et al. used restriction endonucleases and restriction fragment length polymorphism studies to find that certain familial osteoarthritis is associated with abnormalities in COL2AL, the gene encoding type II collagen on the long arm of chromosome 12, where a base at position 519 of the coding alpha chain is mutated and the codon for arginine is codon for cysteine substitution. In addition, mutations in collagen types IV, V, VI and COL9A1 may be susceptibility genes for osteoarthritis. Type II collagen is the main structural component of articular cartilage, accounting for about 85% to 90% of the total. It constitutes the main structure of the matrix network, prevents the expansion of highly hydrated proteoglycans, and is the main matrix for maintaining the normal physicochemical properties and mechanical properties of articular cartilage. Type II collagen is also composed of a homogeneous a. chain, [a1(II)]3, which, like other proteins, is transcribed into mRNA by DNA and then translated and expressed as precollagen Ct peptide in the cell. Many studies have found that a single base mutation in the chain is the genetic basis for the pathogenesis of osteoarthritis, and that structural abnormalities in the gene can cause changes in protein structure, which in turn leads to dyskeletal articular cartilage development. Clinically, this is characterized by premature degeneration and destruction of articular cartilage, followed by osteophytes and other features of primary osteoarthritis. In recent years, many foreign scholars have reported the discovery of type II collagen mutations in several rare scattered families with hereditary chondrodysplasia with OA, a disease whose phenotype is mainly characterized by chondrogenesis imperfecta with secondary manifestations of OA. COL2A1 is located on 12q13.1.13.3 and is approximately 34 kb long, containing 54 exons. Using various experimental molecular biology techniques, especially base sequence determination, 5O mutations in COL2A1 have been identified so far, half of which are single base substitutions, manifesting as a variety of chondrogenesis abnormalities, and the highest mutation rate is thought to be found in its cytosine and guanine duplexes. By studying transgenic mice with abnormal development of the spinal epiphysis, Gaiser et al. found that amino acid substitutions at the Y position on COL2A1 disrupt the triple helix structure of the collagen molecule, resulting in reduced fibril formation and disruption of the structure of cartilage. Type IX collagen was identified 10 years ago as a trace component of cartilage collagen and is composed of three different polypeptide chains that are located on the surface of type II collagen in cartilage and are cross-linked by covalent bonds to bring the two in balance with each other. The position of type IX collagen acts as a bridge between the protofibrils and other macromolecules of the cartilage matrix, thus showing that type IX collagen is important for cartilage adhesion and reversibility. The study of transgenic mice with mutations in the type IX collagen gene revealed that mice with normal maternal development exhibited articular cartilage lesions soon after birth and developed multiple chondrodysplasia with early onset osteoarthritis, suggesting that type IX collagen may be a genetic risk factor for early onset osteoarthritis. COL9A1 was found to be a suspected locus for mutations in hip osteoarthritis in women. Moreover, others have found that mutations in COL9A1, cOIgA2, and COL9A3, located on different chromosomes, can lead to the development of multiple chondrodysplasia, respectively, which is sufficient to support the idea that multiple chondrodysplasia is a heterogeneous disease. However, Aszodi et al. also had a different view, suggesting that the type IX collagen gene is not involved in cartilage formation and its mutation is not a genetic susceptibility factor for osteoarthritis. Pullig et al. found increased expression of type VI collagen in patients with osteoarthritis, suggesting that type VI collagen is involved in the pathogenesis of osteoarthritis. However, some studies have found that type VI collagen mutations are not associated with multiple chondrodysplasias. 3. Apoptosis Programmed death gene 5 (PDCD5) is an apoptosis-related gene identified by the Human Disease Genetic Research Center of Peking University, which plays an important role in apoptosis. Hashimoto et al. Blanco et al. concluded that the degradation of articular cartilage with eventual complete loss is the main pathological feature of osteoarthritis Heraud et al. observed that 18-21% of OA chondrocytes showed apoptotic features in normal and OA femoral articular cartilage, whereas only 2%-5% of normal articular cartilage showed apoptotic cells Cao et al. found that One of the degradation products of proteoglycan polymers, the G1 structural domain, tends to accumulate in synovial fluid and cartilage due to its binding to hyaluronic acid that does not easily enter the circulatory system, and induces chondrocyte apoptosis by reducing intercellular adhesion. Lv Hongbin et al. found that in osteoarthrosis, apoptotic synovial cells appeared, and apoptotic cells were mainly located in the superficial layer, and the apoptosis of synovial cells in diseased joints was much stronger than that in normal tissues. 4, ASPN and GDF-5 Foreign studies have confirmed that the gene (asporin) has a significant correlation with OA. When the deoxyribonucleic acid of the GDF-5 gene is coded as C, it is not prone to morbidity, and when it is coded as T, it is prone to morbidity. In addition, people with a high number of 14 amino acid repeats in the ASPN gene are also susceptible to osteoarthritis. Separate independent studies have been conducted in many countries around the world on populations of different ethnicities. This has revealed the correlation. There are few studies in this area in China, and further studies on the association between asporin gene and OA in the Chinese Han population are needed. Shao Zhenxing et al. investigated the relationship between aspartate(D) repeat sequence polymorphism and osteoarthritis of the knee (OA) in a Chinese Han population. Genotypic determination of D repeat sequence polymorphisms and examination of the relationship between alleles of the repeat sequences were performed in 218 patients with primary symptoms and shadowing evidence of knee OA and 454 age-matched controls. The results showed that D13 and D14 allele frequencies were similar to those of the Japanese population and different from those of the European Caucasian population. the D14 allele was significantly expressed in patients with knee OA (P=0.0013; OR=2.04; 95% CI=1.32 to 3.15). The frequency of D14 was higher in patients with early-onset knee OA than in patients with late-onset OA (P=0.043), and patients with the D14 allele had an earlier age of onset than those without D14 (P=0.028; log-rank time series test). Thus, it was concluded that the D14 allele was significantly associated with susceptibility to knee OA in the Chinese Han population. Since populations in geographic proximity should usually share a similar common ancestor. The HapMap project study has clearly demonstrated many genomic similarities between the Chinese Han Chinese and Japanese populations. 5. HLA-DRB and HLA-A Huang Lihong et al. analyzed the alleles of HLA-DRB and HLA-A in 72 OA patients and 30 healthy controls by using gene microarray technology to explore the relationship between the expression patterns of HLA-DRB and HLA-A gene polymorphisms and clinical characteristics; the results showed that patients with osteoarthritis had HLA-DRB1 12 (DR5), HLA DRB1 08 (DR8), HLA-A0203 (A2) gene expression frequency increased, while HLA-DRB1 53 (DR4) gene expression frequency was significantly reduced; their expression patterns were not related to the involvement site of osteoarthritis patients, but were correlated with the severity of joint damage. Because MHC class I molecules in different individuals present different antigenic fragments to the same macromolecule, thus causing different organisms to show individual differences in immune response to the same antigen. Thus, it is believed that HLA gene polymorphism is closely related to the genetic predisposition to osteoarthritis. 6, vitamin D receptor (VDR) gene The formation of bone redundancy reflects the role of bone metabolism and bone reconstruction, and VDR receptors are found on both osteoblasts and osteoclasts, suggesting that gene polymorphism is most likely related to the formation of bone redundancy. vdr gene may, biologically, increase the density of subchondral bone by adjusting bone density, resulting in minor accumulative damage to articular cartilage locally, thus cause OA. In addition to the above genes. Other genes such as polymerin gene and obesity gene may also be related to the occurrence of osteoarthritis, but it is still difficult to conclude. In conclusion, the etiology of osteoarthritis is multifaceted, among which gene mutations may occupy a more important position in the pathogenesis. Therefore, further studies are needed.