Table 2. 25 polymorphic SNPs identified during DNA sequencing of 40 controls and 10 cases.
Gene Loci | Genotype Frequency In Our Study (%) | CA Trend | Fishers-Exact | ||||||||
According To | rs | MOR | AA | Homozygous | Homozygous | Test | Test | ||||
SNP | MOR11 | Number | Transcript | Change | Patients | Major3 | Heterozygote3 | Minor3 | p-value4 | MAF | p-value4 |
1 | 5′UR/T-2694G 2 | rs12210856 | - | Cases | 90.00 | 10.00 | - | 0.197 | 5.00 | 0.46 | |
Controls | 70.00 | 30.00 | - | 15.00 | |||||||
2 | 5′UR/A-2455C | rs12190259 | - | Cases | 90.00 | 10.00 | - | 0.197 | 5.00 | 0.46 | |
Controls | 70.00 | 30.00 | - | 15.00 | |||||||
3 | 5′UR/G-1509A | rs12205732 | - | Cases | 90.00 | 10.00 | - | 0.197 | 5.00 | 0.46 | |
Controls | 70.00 | 30.00 | - | 15.00 | |||||||
4 | 5′UTR/G-172T | rs6912029 | MOR1 | Cases | 90.00 | 10.00 | - | 0.156 | 5.00 | 0.29 | |
Controls | 67.50 | 32.50 | - | 16.25 | |||||||
5 | E1/A118G | rs1799971 | MOR1 | Asn→Asp | Cases | 30.00 | 70.00 | - | 0.643 | 35.00 | 0.80 |
Controls | 32.50 | 55.00 | 12.50 | 40.00 | |||||||
6 | I1/G-2994A | rs563649 | MOR1K1 | Cases | 90.00 | 10.00 | - | 0.247 | 5.00 | 0.45 | |
5′UTR | Controls | 72.50 | 27.50 | - | 13.75 | ||||||
7 | I1/G -2259A | rs9322446 | MOR1K1 | Cases | 90.00 | 10.00 | - | 1.000 | 5.00 | 1.00 | |
5′UTR | Controls | 90.00 | 10.00 | - | 5.00 | ||||||
8 | E3/G877A | NV1 | MOR1 | Val→Ile | Cases | 100.00 | 0.00 | - | 0.471 | 0.00 | 1.00 |
Controls | 95.00 | 5.00 | - | 2.50 | |||||||
9 | I3/G399T | NV2 | MOR1A | Cases | 90.00 | 10.00 | - | 0.043 | 5.00 | 0.20 | |
3′UTR | Controls | 100.00 | 0.00 | - | 0.00 | ||||||
10 | I3/A1839T | rs540825 | MOR1X | Glu→His | Cases | 60.00 | 40.00 | - | 0.002 * (0.035 * ) | 20.00 | 0.01 * (0.15) |
E4 | Controls | 95.00 | 5.00 | - | 2.50 | ||||||
11 | I3/C1956T | rs675026 | MOR1X | Gly→Gly | Cases | 60.00 | 30.00 | 10.00 | 0.030* (0.456) | 25.00 | 0.04* (0.60) |
E4 | Controls | 87.50 | 10.00 | 2.50 | 7.50 | ||||||
12 | I3/A1966G | rs562859 | MOR1X | Leu→Leu | Cases | 70.00 | 20.00 | 10.00 | 0.103 | 20.00 | 0.11 |
E4 | Controls | 87.50 | 10.00 | 2.50 | 7.50 | ||||||
13 | I3/C-11152T | NV3 | MOR1B5 | Glu→Stop | Cases | 60.00 | 40.00 | - | 0.042* (0.633) | 20.00 | 0.05 |
Controls | 92.50 | 5.00 | 2.50 | 5.00 | |||||||
14 | I3/C18957T | rs606545 | MOR1B1 | Cases | 60.00 | 40.00 | - | 0.042* (0.633) | 20.00 | 0.05 | |
3′UTR | Controls | 92.50 | 5.00 | 2.50 | 5.00 | ||||||
15 | 3′UTR/A725G | rs17181352 | MOR1 | Cases | 100.00 | 0.00 | - | 0.614 | 0.00 | 1.00 | |
Controls | 97.50 | 2.50 | - | 1.25 | |||||||
16 | 3′DR/A148G | rs671531 | - | Cases | 80.00 | 20.00 | - | 0.459 | 10.00 | 0.60 | |
Controls | 92.50 | 5.00 | 2.50 | 5.00 | |||||||
17 | 3′DR/A633G | rs583664 | - | Cases | 70.00 | 30.00 | - | 0.158 | 15.00 | 0.14 | |
Controls | 92.50 | 5.00 | 2.50 | 5.00 | |||||||
18 | 3′DR/C932T | rs658156 | - | Cases | 60.00 | 40.00 | - | 0.042* (0.633) | 20.00 | 0.05 | |
Controls | 92.50 | 5.00 | 2.50 | 5.00 | |||||||
19 | 3′DR/G971A | rs9371776 | - | Cases | 100.00 | - | - | 0.372 | - | 1.00 | |
Controls | 92.50 | 7.50 | - | 3.75 | |||||||
20 | 3′DR/G1270A | rs558948 | - | Cases | 60.00 | 40.00 | - | 0.042* (0.633) | 20.00 | 0.05 | |
Controls | 92.50 | 5.00 | 2.50 | 5.00 | |||||||
21 | 3′DR/T1371C | rs558025 | - | Cases | 60.00 | 40.00 | - | 0.042* (0.633) | 20.00 | 0.05 | |
Controls | 92.50 | 5.00 | 2.50 | 5.00 | |||||||
22 | 3′DR/C1510T | rs645027 | - | Cases | 80.00 | 20.00 | - | 0.44 | 10.00 | 0.73 | |
Controls | 67.50 | 32.50 | - | 16.25 | |||||||
23 | 3′DR/C1549T | rs598160 | - | Cases | 60.00 | 40.00 | - | 0.042* (0.633) | 20.00 | 0.05 | |
Controls | 92.50 | 5.00 | 2.50 | 5.00 | |||||||
24 | 3′DR/C1657G | rs644261 | - | Cases | 60.00 | 40.00 | - | 0.042* (0.633) | 20.00 | 0.05 | |
Controls | 92.50 | 5.00 | 2.50 | 5.00 | |||||||
25 | 3′DR/G1665A | NV4 | - | Cases | 100.00 | - | - | 0.614 | - | 1.00 | |
Controls | 97.50 | 2.50 | - | 1.25 |
Footnote: SNP 10, rs540825, was significantly associated with fentanyl-induced emesis pre- and post- Bonferroni correction.
Abbreviations: SNP: Single nucleotide polymorphism; UR: Upstream region; DR: Downstream region;
UTR: Untranslated region; E: Exon; I: Intron; NV: Novel variant; MOR: Mu opioid receptor;
NCBI: National Centre For Biotechnology Information; CA: Cochran-Armitage; AA: Amino acid;
MAF: Minor allele frequency; Asn: Asparigine; Asp: Aspartate; Val: Valine; Ile: Isoleucine;
Glu: Glutamine; His: Histidine; Gly: Glycine; Leu: Leucine.
Legends:
MOR1 is the main transcript of OPRM1. Other transcripts of MOR1 e.g. MOR1X and MOR1K1 are splice variants of MOR.
The letter in capitals refers to the minor allele of the SNP.
Patients with 2 copies of the major or minor allele respectively. Heterozygote: Patients with 1 copy each of the major and minor allele.
Non-bracketed p-values for the CA trend test and Fishers-Exact test refers to p-values before Bonferroni correction. Bracketed (p-values) refers to p-values post-Bonferroni correction.
p-value<0.05 indicates statistical significance.