Table 2.
Other Genes Associated with XFS/XFG Disease Risk
| Gene | Gene Function |
Chromosomal Location |
Study Design | Population | Number of Cases/ Number of Controls |
Significant Association? | Reference(s) |
|---|---|---|---|---|---|---|---|
| Contactin- associated protein- like 2 (CNTNAP |
Potassium channel trafficking and membrane stabilization |
7q35-q36 | GWAS | German Italian |
160 / 80, 610 / 364 (2 independent cohorts) 249 / 190 |
Yes No |
64 |
| Replication study | Japanese | 108 / 199 | Yes | 65 | |||
| Replication study | Polish | 48 / 30 | No | 66 | |||
| Clusterin (CLU) | Apoptosis, inhibition of stress- induced protein aggregation |
8p21 | Candidate gene study |
Australian | 86 / 2422 | Yes (though not significant after controlling for age) |
67 |
| Candidate gene study |
German Italian |
333 / 342, 328 / 342 (2 cohorts) 209 / 190 |
Yes No |
68 | |||
| Apolipoprotein E (APOE) |
Amyloid deposition and fibril formation |
19q13.2 | Candidate gene study |
Turkish | 76 / 74 | Yes | 69 |
| Candidate gene study |
German Italian |
661 / 342 209/190 |
No No |
70 | |||
| Candidate gene study |
Greek | 151 / 107 | No | 71 | |||
| Glutathione-S- transferase genes (GSTs) |
Protect cells from oxidative stress |
Multiple chromosomal loci |
Candidate gene study |
Swedish | 188 / 200 | No | 72 |
| Candidate gene study |
Turkish | 60 / 65 | No | 73 | |||
| Candidate gene study |
Pakistani | 165 / 162 | Yes (association only seen in female patients, not males) |
74 | |||
| TNF-α | Pro- inflammatory cytokine |
6p21.3 | Candidate gene study |
Pakistani | 122 / 126 | Yes | 75 |
| Candidate gene study |
Iranian | 223 / 202 | Yes | 76 | |||
| Candidate gene study |
Caucasian | 204 / 204 | No | 77 | |||
| Candidate gene study |
Turkish | 110 / 110 | No | 78 | |||
| Meta-analysis | Multiple (14 studies included) |
1182 / 3003 | No | 79 | |||
| Methylene- tetrahydrofolate reductase (MTHFR) |
Folate and amino acid metabolism |
1p36.3 | Candidate gene study |
Turkish | 76 / 34 | No | 80 |
| Candidate gene study |
Greek | 151 / 107 | No | 71 | |||
| Candidate gene study |
U.S. Caucasian | 140 / 127 | No | 81 | |||
| Candidate gene study |
Central European | 138 / 211 | No | 82 | |||
| Candidate gene study |
German | 71 / 71 | No | 83 | |||
| Candidate gene study |
Iranian | 85 / 908382828281 | No | 84 | |||
| Matrix metalloproteinases (MMPs) |
Extracellular matrix turnover |
Multiple chromosomal loci |
Candidate gene study |
Greek | 182 / 214 | Yes (though not significant after adjusting for multiple comparisons) |
85 |
| Candidate gene study |
Caucasian | 202 / 248 | No | 86 | |||
| Latent TGF-β binding protein 2 (LTBP2) |
Structural component of microfibrils |
14q24.3 | Candidate gene study |
Iranian | 48 / None | Yes | 87 |
| Candidate gene study |
German | 333 / 342 | No | 68 |
In addition to LOXL1, several other genes have been found to be associated with XFS/XFG risk. However, variants in these genes demonstrate association in only a limited number of populations, suggesting that these associations are either weak or are confined to specific ethnic groups.