Association of the functional A118G polymorphism of OPRM1 in diabetic patients with foot ulcer pain
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.
aGraduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
bDepartment of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
cFaculty of Medicine, Department of Anesthesiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
dDepartment of Medical Research, Fooyin University and Hospital, Kaohsiung, Taiwan
eDepartment of Microbiology, Kaohsiung Medical University, Kaohsiung, Taiwan
fDivision of General and Gastroenterologic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
gFaculty of Medicine, Department of Surgery, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
hGraduate Institute of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
iDivision 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.
1 Chung-Sheng Lai and Jaw-Yuan Wang contributed equally to this article.
ABSTRACT