# Follow-up of GSTM1, GSTT1, and NAT2 genotyped patients with knee or hip replacement

**Authors:** Selahattin Bozkurt, Silvia Selinski, Meinolf Blaszkewicz, Jörg Reinders, Jan G. Hengstler, Lukas Niggemann, Klaus Golka

PMC · DOI: 10.17179/excli2025-8565 · EXCLI Journal · 2025-06-18

## TL;DR

This study followed patients with knee or hip replacements and found a lower rate of a specific gene variant compared to controls, suggesting potential relevance to implant outcomes.

## Contribution

The study reports a lower proportion of GSTM1-negative genotype in joint replacement patients compared to controls, prompting further investigation into its clinical relevance.

## Key findings

- GSTM1-negative genotype was less common in patients (45%) than in controls (51-52%).
- Follow-up after 9 years failed to clarify the clinical significance of the GSTM1-negative genotype.
- The GSTM1-negative genotype proportion in followed-up patients matched the initial collective.

## Abstract

A total of 147 patients, genotyped for glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and for N-acetyltransferase 2 (NAT2), who had undergone total joint replacement of the knee or hip joint between August 2004 and June 2007, showed with 45% a remarkably lower portion of the GSTM1-negative genotype compared to both a local control (51%), an external control (52%) and the portion reported in the literature for the European population (50%). In contrast, the portions of GSTT1-positive (84%) and slow NAT2 (55.1%) patients of the initial collective were unremarkable, compared to both controls. To elucidate a possible impact of this interesting finding on the long-term outcome, the patients were contacted in December 2015. Afterwards, they were interviewed using a self-prepared questionnaire. The average follow-up time was 9 years. At the time of follow-up, 57 patients were deceased, 46 patients did not respond and 12 patients declined the interview. A total of 32 patients participated in the follow-up. The mean age of the followed-up patients was 75.9±8.3 years, whereas the mean age of all patients at the time of surgery was 70.9±9 years. The portions of the GSTM1-negative genotype (15 out of 32; 47%), the GSTT1-positive genotype (24 out of 32; 75%) and the slow NAT2 status (17 out of 32; 53%) in the followed-up patients were comparable to those of the initial collective. The follow-up results of the patients after 9 years were unable to clarify the significance of the observed lower portion of GSTM1-negative patients. In view of a recently published omics study reporting a reduced GSTM1 activity in tissue attached on hip implants explanted due to aseptic loosening, the striking portion of the GSTM1-negative genotype in this present study may encourage further investigation into the impact of this gene in patients with hip or knee replacement.

## Linked entities

- **Genes:** GSTM1 (glutathione S-transferase mu 1) [NCBI Gene 2944], GSTT1 (glutathione S-transferase theta 1) [NCBI Gene 2952], NAT2 (N-acetyltransferase 2) [NCBI Gene 10]

## Full-text entities

- **Genes:** NAT2 (N-acetyltransferase 2) [NCBI Gene 10] {aka AAC2, NAT-2, PNAT}, GSTM1 (glutathione S-transferase mu 1) [NCBI Gene 2944] {aka GST1, GSTM1-1, GSTM1a-1a, GSTM1b-1b, GTH4, GTM1}, GSTT1 (glutathione S-transferase theta 1) [NCBI Gene 2952]
- **Diseases:** aseptic loosening (MESH:D011475)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12235267/full.md

## References

66 references — full list in the complete paper: https://tomesphere.com/paper/PMC12235267/full.md

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Source: https://tomesphere.com/paper/PMC12235267