Genetic association of the COL1A1 gene promoter –1997 G/T (rs1107946) andSp1 +1245 G/T (rs1800012) polymorphisms and keloid scars in a Jeddah population

Abstract

IntroductionKeloid scars are benign fibroproliferative cutaneous lesions resulting from the overproduction of all components of the healing process, including fibroblasts, collagen, elastin, and proteoglycans; they can occur following burn injuries, lacerations, abrasions, surgery, piercings, vaccinations, and even minor skin trauma. They are unique in humans, and especially in genetically susceptible individuals from nonwhite populations (1-3). It has been estimated that about 15%-20% of Blacks, Hispanics, and Orientals suffer from keloids and there appears to be a genetic predisposition to keloid formation (4). Keloids can develop at every age, but they have a higher incidence between 10 and 30 years (1,3). A slight female predominance is also noted, but this could be related to the higher rate of earlobe piercing in females (3,5). The incidence rates of hypertrophic scarring vary from 40% to 70% following surgery to up to 91% following burn injuries (4). The alterations responsible for keloid formation are still unknown, but it is thought that Background/aim: Scars develop at the end of the natural wound-healing process and are characterized by excessive collagen deposition, particularly types I and III collagen. This study aimed to investigate the genetic association of COL1A1 −1997 G/T (rs1107946) and COL1A1 Sp1 +1245 G/T (rs1800012) polymorphisms with the incidence of scars. Materials and methods:A case-control association study was conducted with 84 volunteers from Jeddah, Saudi Arabia (47 patients and 37 controls). The allele frequency distribution and nucleotide genotypes of −1997 G/T, +1245 G/T were ascertained by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis.Results: Our results indicated that the distribution of COL1A1 (rs1107946) genotypes was significantly different between patients and controls (P = 0.00). The incidence of COL1A1 (rs1107946) genotype GG was significantly associated with a risk of scars. The distribution of the (rs1107946) genotype was drastically higher in women with scars (P= 0.00). One haplotype block in COL1A1 was documented by the pair-wise linkage disequilibrium between the single nucleotide polymorphisms (SNPs). The frequency of the GG haplotype constructed by the two SNPs was robustly high and associated with risk of scars. Conclusion:Our results strengthen the evidence for the association between polymorphisms of −1997 G/T, +1245 G/T of the COL1A1 gene in the genetic etiology of keloid scars.

The m6A demethylase FTO promotes keloid formation by up-regulating COL1A1

“…In this study, the expression changes of the m6A modification site of COL1A1 and the stability of COL1A1 mRNA were shown to mediate the regulatory effect of FTO on keloids. Previous study has demonstrated gene promoters showed a strong positive connection with the risk of keloid formation (14). Wang et al found that COL1A1 mediates the promotion of H19 on the proliferation and metastasis of skin fibroblasts (15).…”

“…Previous study has demonstrated that COL1A1 can promote the formation of keloids since excessive collagen deposition is an essential characteristic of keloids. A Linjawi et al discovered that the COL1A1 −1,997 G/T (rs1107946) and Sp1 +1,245 G/T (rs1800012) gene promoters showed a strong positive connection with the risk of keloid formation ( 14 ). Wang et al found that COL1A1 mediates the promotion of H19 on the proliferation and metastasis of skin fibroblasts ( 15 ).…”

Prediction and association analyses of skin phenotypes in Japanese females using genetic, environmental, and physical features

“…MMP‐1 rs1799750 is known to increase the expression of MMP‐1 and is indicative of susceptibility to skin aging 50 . It has also been reported that the G allele of COL1A1 rs1107946 enhances the production of α1 chain of type I collagen, affects the balance with α2 chain, changes the quality of the collagen chain, and promotes keloid formation 51 . The hardness of dermal collagen fibers may affect facial recovery and flexibility after skin deformation due to facial expressions such as laughing, which may promote transient wrinkle formation.…”

MicroRNA-98 inhibits the cell proliferation of human hypertrophic scar fibroblasts via targeting Col1A1

“…Some studies showed when ECM proteins (such as pro-Col1A1) increased, the excessive scar fibrosis occurred [31]. Scars are characterized by excessive collagen deposition, particularly types I and III collagen [32]. …”