Combined Effects of MMP-7, MMP-8 and MMP-26 on the Risk of Ischemic Stroke
Abstract
:1. Introduction
2. Research Design and Methods
2.1. Study Population
2.2. Data Collection
2.3. Genomic DNA Isolation and Genotyping of MMP-7, MMP-8 and MMP-26
2.4. Weighted Genetic Risk Score of MMP-7, MMP-8 and MMP-26
2.5. Statistical Analysis
3. Results
3.1. Basic Characteristics of Ischemic Stroke Cases and Controls
3.2. Association Between Selected SNPs and Risk of Ischemic Stroke Risk
3.3. Association Between wGRS and Risk of Ischemic Stroke Risk
3.4. Association Between wGRS and Risk of Ischemic Stroke Risk in Subgroup Analysis
3.5. Interaction Between High wGRS and Greater Number of Modifiable Cardiovascular Disease Risk Factors on the Risk of Ischemic Stroke
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A
Genotyping of MMP-7, MMP-8 and MMP-26
SNP | Primer (5′→3′) a | PCR Condition | RFLP Condition | Product Size (bp) | ||||
---|---|---|---|---|---|---|---|---|
Temp (°C) | Time | Cycles | Restriction Enzyme | Temp (°C) | Time | |||
rs3740938 | F: TGTTTCAGCTATGGGGTTCC R: TCAAGCAACCCTATCCAACC | 95 | 30′ | 35 | BtgI | 37 | 1 h | GG: 388, 88 |
57.4 | 30′ | GA: 487, 399, 88 | ||||||
72 | 30′ | AA: 487 | ||||||
rs1940475 | F: TGGAAAGAACCCACGGTATC R: ACAGCAAGACCCCTATGTGC | 95 | 30′ | 35 | BccI | 37 | 4 h | CC: 276, 182 |
58.1 | 30′ | CT: 458, 276, 182 | ||||||
72 | 30′ | TT: 458 | ||||||
rs11225395 | F: TTGTATGGGGCCTAGAGCTG R: CTCATTCTCCCTCTCCCTTG | 95 | 30′ | 35 | SfcI | 37 | 4 h | CC: 358, 132, |
59.2 | 30′ | CT: 490, 358, 132 | ||||||
72 | 30′ | TT: 490 | ||||||
rs11568818 | F: TGGTACCATAATGTCCTGAATG R: TCGTTATTGGCAGGAAGCACACAATGAATT | 95 | 30′ | 35 | EcoRI-HF | 37 | 1 h | AA: 150 |
59.3 | 30′ | AG: 150, 120, 30 | ||||||
72 | 30′ | GG: 120, 30 | ||||||
rs2499966 | F: GATTAGGAATAGACCTTTGCATTTTCGTAC R: GACTTAACCAAAGTTTCATAGC | 95 | 30′ | 35 | Hpy166Ц | 37 | 0.5h | CC: 114, 29 |
58 | 30′ | CA: 143, 114, 29 | ||||||
72 | 30′ | AA: 143 |
SNP | Primer (5′→3′) a | PCR Condition | Product Size (bp) | ||
---|---|---|---|---|---|
Temp (°C) | Time | Cycles | |||
rs10502001 | F1: GCCAATCATGATGTCAGCAG R1: CCTATAACTGGAATGTTAAACTCGCA F2: GGCTTCTGCATTATTTCTATGAGGC R2: ACAGGAACCAAAGGCAAGAG | 95 | 30′ | 35 | CC: 537, 236 |
64 | 30′ | CT: 537, 345, 236 | |||
72 | 30′ | TT: 537, 345 | |||
rs2499953 | F1: GTACCGTCCTTCTGAGACC R1: GGAGTGGCGACTCCTTGTT F2: TTTCCATCAATTTTTCCTGAGCG R2: GCTGCCAATGAAAGCAGAA | 95 | 30′ | 35 | AA: 434, 149 |
53.7 | 30′ | AG: 434, 326, 149 | |||
72 | 30′ | GG: 434, 326 |
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Variables a | Cases N = 500 | Controls N = 500 | p Value b |
---|---|---|---|
Age | 61.33 ± 11.07 | 61.17 ± 10.99 | 0.8085 |
Males | 333 (66.60) | 333 (66.60) | 1.0000 |
Smoking | 241 (48.59) | 154 (30.86) | <0.0001 |
Alcohol drinking | 105 (21.13) | 67 (13.40 ) | 0.0012 |
Hypertension | 374 (74.80) | 263 (52.60) | <0.0001 |
Diabetes | 227 (45.40) | 83 (16.60) | <0.0001 |
Hyperlipidemia | 414 (82.97) | 405 (81.00) | 0.4189 |
Obesity | 143 (29.61) | 99 (20.00) | 0.0005 |
Gene | rs Number a | Region | Risk Allele | Risk Allele Frequency | Other Allele | Additive Model | Dominant Model | Recessive Model |
---|---|---|---|---|---|---|---|---|
aOR (95%CI) b | aOR (95%CI) b | aOR (95%CI) b | ||||||
MMP-7 | rs10502001 | 11q22.2 | C | 0.72 | T | 1.06 (0.83–1.35) | 1.79 (1.01–3.16) c | 0.93 (0.68–1.26) |
MMP-7 | rs11568818 | 11q22.2 | G | 0.08 | A | 0.98 (0.65–1.46) | 1.00 (0.65–1.55) | 0.58 (0.09–3.56) |
MMP-8 | rs3740938 | 11q22.2 | A | 0.25 | G | 1.02 (0.80–1.30) | 0.87 (0.64–1.18) | 1.92 (1.03–3.58) c |
MMP-8 | rs1940475 | 11q22.2 | C | 0.60 | T | 1.11 (0.89–1.39) | 1.06 (0.69–1.62) | 1.20 (0.87–1.66) e |
MMP-8 | rs11225395 | 11q22.2 | T | 0.39 | C | 1.02 (0.81–1.28) | 0.94 (0.68–1.29) | 1.24 (0.79–1.93) e |
MMP-26 | rs2499953 | 11p15.4 | G | 0.30 | A | 1.00 (0.78–1.26) | 0.99 (0.73–1.35) | 1.00 (0.58–1.72) |
MMP-26 | rs2499966 | 11p15.4 | C | 0.75 | A | 1.27 (0.98–1.63) d | 0.82 (0.43–1.56) | 1.49 (1.10–2.04) c |
Variables | Adjusted-OR a (95% CI) |
---|---|
Smoking | |
No | 1.00 (ref.) |
Yes | 2.54 (1.81–3.56) c |
Alcohol drinking | |
No | 1.00 (ref.) |
Yes | 1.40 (0.95–2.07) |
Obesity | |
No | 1.00 (ref.) |
Yes | 1.31 (0.94–1.81) |
Hypertension | |
No | 1.00 (ref.) |
Yes | 2.38 (1.75–3.24) c |
Diabetes | |
No | 1.00 (ref.) |
Yes | 3.63 (2.66–4.95) c |
wGRS b | |
<0.764 | 1.00 (ref.) |
0.764–0.981 | 1.50 (1.08–2.08) c |
≥ 0.981 | 1.59 (1.09–2.32) c |
Variables | Ca/Co | Adjusted OR (95% CI) a | ||
---|---|---|---|---|
wGRS <0.764 | wGRS ≥0.764 | |||
Age | ≦55 | 149/151 | 1.00 (ref) | 1.38 (0.75–2.53) |
>55 | 329/343 | 1.00 (ref) | 1.62 (1.13–2.33) b | |
sex | Female | 158/164 | 1.00 (ref) | 1.44 (0.83–2.50) |
Male | 320/330 | 1.00 (ref) | 1.60 (1.10–2.33) b | |
Smoking | No | 244/343 | 1.00 (ref) | 1.57 (1.04–2.36) b |
Yes | 234/151 | 1.00 (ref) | 1.46 (0.91–2.35) | |
Alcohol drinking | No | 376/427 | 1.00 (ref) | 1.57 (1.11–2.20) b |
Yes | 102/67 | 1.00 (ref) | 1.41 (0.68–2.93) | |
Hypertension | No | 117/234 | 1.00 (ref) | 1.15 (0.64–2.06) |
Yes | 361/260 | 1.00 (ref) | 1.68 (1.17–2.42) b | |
Diabetes | No | 261/411 | 1.00 (ref) | 1.45 (1.00–2.09) b |
Yes | 217/83 | 1.00 (ref) | 1.77 (1.01–3.10) b | |
Obesity | No | 335/395 | 1.00 (ref) | 1.53 (1.07–2.21) b |
Yes | 143/99 | 1.00 (ref) | 1.39 (0.78–2.48) |
Subgroup | Ca/Co | Adjusted-OR (95% CI) c | S (95% CI) | RERI (95% CI) | AP (95% CI) |
---|---|---|---|---|---|
Low genetic risk (wGRS<0.764) | |||||
Low modifiable CVD risk a | 32/85 | 1.00 (ref) | |||
High modifiable CVD risk b | 96/78 | 3.59 (2.15–6.00) | 1.65(0.99–2.73) | 1.87(0.16–3.57) d | 0.33(0.07–0.58) d |
High genetic risk (wGRS≧0.764) | |||||
Low modifiable CVD risk a | 95/201 | 1.29 (0.80–2.08) | |||
High modifiable CVD risk b | 255/130 | 5.75 (3.60–9.19) |
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Hsieh, F.-I.; Chiou, H.-Y.; Hu, C.-J.; Jeng, J.-S.; Lin, H.-J.; Lee, J.-T.; Lien, L.-M. Combined Effects of MMP-7, MMP-8 and MMP-26 on the Risk of Ischemic Stroke. J. Clin. Med. 2019, 8, 2011. https://doi.org/10.3390/jcm8112011
Hsieh F-I, Chiou H-Y, Hu C-J, Jeng J-S, Lin H-J, Lee J-T, Lien L-M. Combined Effects of MMP-7, MMP-8 and MMP-26 on the Risk of Ischemic Stroke. Journal of Clinical Medicine. 2019; 8(11):2011. https://doi.org/10.3390/jcm8112011
Chicago/Turabian StyleHsieh, Fang-I, Hung-Yi Chiou, Chaur-Jong Hu, Jiann-Shing Jeng, Huey-Juan Lin, Jiunn-Tay Lee, and Li-Ming Lien. 2019. "Combined Effects of MMP-7, MMP-8 and MMP-26 on the Risk of Ischemic Stroke" Journal of Clinical Medicine 8, no. 11: 2011. https://doi.org/10.3390/jcm8112011
APA StyleHsieh, F.-I., Chiou, H.-Y., Hu, C.-J., Jeng, J.-S., Lin, H.-J., Lee, J.-T., & Lien, L.-M. (2019). Combined Effects of MMP-7, MMP-8 and MMP-26 on the Risk of Ischemic Stroke. Journal of Clinical Medicine, 8(11), 2011. https://doi.org/10.3390/jcm8112011