Association of the functional A118G polymorphism of OPRM1 in diabetic patients with foot ulcer pain

Cheng, Kuang-I; Lin, Shiu-Ru; Chang, Lin-Li; Wang, Jaw-Yuan; Lai, Chung-Sheng

doi:10.1016/j.jdiacomp.2009.02.003

« Previous Next »Journal of Diabetes and Its Complications
Volume 24, Issue 2 , Pages 102-108, March 2010

Association of the functional A118G polymorphism of OPRM1 in diabetic patients with foot ulcer pain

Kuang-I Cheng
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Medicine, Department of Anesthesiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Shiu-Ru Lin
- Department of Medical Research, Fooyin University and Hospital, Kaohsiung, Taiwan
Lin-Li Chang
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Microbiology, Kaohsiung Medical University, Kaohsiung, Taiwan
Jaw-Yuan Wang
- Division of General and Gastroenterologic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Medicine, Department of Surgery, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Corresponding authors. Faculty of Medicine, Department of Surgery, College of Medicine, Kaohsiung Medical University, 100 Shin-Chuan 1st Road, Kaohsiung 807, Taiwan. Tel.: +886 7 3121101x7676; fax: +886 7 3111482.
- Chung-Sheng Lai and Jaw-Yuan Wang contributed equally to this article.
Chung-Sheng Lai
- Faculty of Medicine, Department of Surgery, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Corresponding authors. Faculty of Medicine, Department of Surgery, College of Medicine, Kaohsiung Medical University, 100 Shin-Chuan 1st Road, Kaohsiung 807, Taiwan. Tel.: +886 7 3121101x7676; fax: +886 7 3111482.
- Chung-Sheng Lai and Jaw-Yuan Wang contributed equally to this article.

Received 30 July 2008; received in revised form 22 December 2008; accepted 4 February 2009. published online 23 March 2009.

Abstract

Background

Diabetic foot ulcer (DFU) patients may experience moderate or severe pain. A single-nucleotide polymorphism, at nucleotide 118 for opioid receptor mu 1 (OPRM1), has been reported to alter the opioid effects to relieve acute or chronic pain. The purpose of this study was to elucidate the correlation between nucleotide 118 variants and foot ulcer pain in DFU patients.

Methods

Sixty-five DFU patients with Grade 2–5 Wagner–Meggitt classification were enrolled. The occurrence of pain in activities was categorized into five grades. Patients were allocated either into the painless DFU group, with a visual analog scale (VAS) pain score ≦3, or into the painful DFU group, with a VAS pain score ≧4 and Grades 3–5 of occurrence of pain in daily activities. DNA was extracted from blood samples of analyzed patients. Using the polymerase chain reaction–single-strand conformation polymorphism analysis and DNA sequencing of nucleotide 118, we identified the genotype distribution and allelic frequencies in DFU patients. The sequences of the forward and the reverse primer are designed as follows: 5′-TAATACGACTCACTATAGGG-3′ and 5′-ACGCACACGATGGAGTAGAG-3′, respectively.

Results

Fifteen patients were classified into the painful DFU group and 50 patients were classified into the painless DFU group. The amplified DNA fragments showed 26 homozygous (AA), 34 heterozygous (AG), and 5 mutant homozygous (GG) genotypes, with overall A and G allelic frequencies of 66.2% and 33.8%, respectively. The painful DFU group included 10 AA subjects, 4 AG subjects, and 1 GG subject, while the painless DFU group had 16 AA, 30 AG, and 4 GG subjects (P=.038).

Conclusion

The A118G polymorphism of mu-opioid receptor may be closely associated with DFU pain in 34 out of 50 patients in the painless group and in 5 out of 15 patients in the painful group. This indicates that the nucleotide 118 variant patients may suffer less DFU pain.

Keywords: Diabetes, Single-nucleotide polymorphism, Mu-opioid receptor, OPRM1, Foot ulcer pain