Characteristics of acetylation reactions in patients with stenosing process of the lumbar spinal canal and dural sac depending on severity of Ligamentum flavum ossification

Abstract

Background. Expression of acetyltransferase genes in structures participating in formation of a pathological focus in development of degenerative spine conditions is presently unstudied. Hypertrophy and ossification of Ligamentum flavum play a leading role in the development and progression of stenosing processes in the spinal canal and dural sac whereas acetyltransferases are involved in metabolism of connective tissue. The aim of this study was to identify genetic characteristics of acetylation reactions in patients with stenosis of the lumbar spinal canal and dural sac depending on severity of ossification of Ligamentum flavum.
Methods. This study included 31 patients (15 men and 16 women aged 45.7 ± 2.0 years) with stenosing processes of the spinal canal and dural sac at the lumbar level. Samples of Ligamentum flavum were taken from all patients at the time of surgical intervention. Signs of hypertrophy and/or ossification were detected in these samples with standard pathomorphological methods. Real time PCR was used to determine the expression of NAT1 and NAT2 genes.
Results. Expression of NAT1 and NAT2 genes was found in biopsy samples of Ligamentum flavum. This indicated a previously unknown role of acetylation processes in connective tissue metabolism. Variants of «slow» acetylation were significantly more common in patients with documented ossification of Ligamentum flavum. Different patterns of NAT1 and NAT2 gene expression were identified, which suggested polymorphism of clinical variants of the disease. Some of the identified variants of acetyltransferase isoenzyme expression characterize a tendency towards development of Ligamentum flavum ossification. Women were more likely to have ossification of Ligamentum flavum than men (χ2 = 39.1, p < 0.01). Repeated surgery and overweight did not increase the risk for ossification of Ligamentum flavum. The activity of NAT2 gene expression can be classified as an informative
marker for increased risk of ectopic ossification of Ligamentum flavum.
Conclusion. The identified patterns of acetylation reactions in patients with spinal canal and dural sac stenosis may help clinicians to predict the development of hypertrophy and ossification of Ligamentum flavum during spine surgery and to find ways for prevention of epidural fibrosis at the preoperative stage.