Apolipoproteine and KLOTHO Gene Variants Do Not Affect the Penetrance of Fragile X-Associated Tremor/Ataxia Syndrome
Abstract
1. Introduction
2. Results
2.1. FXTAS Stage by APOε4 and KLOTHO Variant Genotypes
2.2. FXTAS Diagnosis by APOε4 and KLOTHO Variant Genotype
2.3. FXTAS Stage and Diagnosis by APOε2 and ε4 Alleles
2.4. Changes Overtime in VIQ by APOε2 and ε4 Among FXTAS Subjects
2.5. No Changes Overtime in PIQ and FSIQ by APOε2 and ε4 Alleles among FXTAS Subjects
3. Discussion
4. Materials and Methods
4.1. Participants
4.2. Molecular Measures
4.3. Clinical Measures
4.4. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | Overall (n = 245) |
---|---|
Age | |
Mean (SD) | 66.1 (7.93) |
Median [Min, Max] | 66.0 [50.0, 89.0] |
Race | |
American Indian/Alaska Native | 3 (1.2%) |
Asian | 1 (0.4%) |
More Than One Race | 1 (0.4%) |
Unknown | 34 (13.9%) |
White | 206 (84.1%) |
Ethnicity | |
Hispanic or Latino | 10 (4.1%) |
Non-Hispanic or Latino | 180 (73.5%) |
Unknown | 55 (22.4%) |
CGG repeats | |
Mean (SD) | 86.9 (18.8) |
Median [Min, Max] | 84.0 [52.0, 183] |
Missing | 1 (0.4%) |
AGG Interruptions | |
0 | 122 (49.8%) |
1 | 76 (31.0%) |
2 | 47 (19.2%) |
APOε | |
ε2,ε2 | 3 (1.2%) |
ε2,ε3 | 25 (10.2%) |
ε2,ε4 | 6 (2.4%) |
ε3,ε3 | 163 (66.5%) |
ε3,ε4 | 47 (19.2%) |
ε4,ε4 | 1 (0.4%) |
KLOTHO | |
KL-VShet− | 166 (67.8%) |
KL-VShet+ | 69 (28.2%) |
KL-hom+ | 10 (4.1%) |
FXTAS Stage | |
0 | 14 (5.7%) |
1 | 20 (8.2%) |
2 | 44 (18.0%) |
3 | 64 (26.1%) |
4 | 39 (15.9%) |
5 | 18 (7.3%) |
Missing | 46 (18.8%) |
FXTAS Diagnosis | |
No | 25 (10.2%) |
Possible | 34 (13.9%) |
Probable | 37 (15.1%) |
Definite | 103 (42.0%) |
Missing | 46 (18.8%) |
FXTAS (n = 165) | No FXTAS (n = 34) | No Diagnosis (n = 46) | Overall (n = 245) | |
---|---|---|---|---|
Age | ||||
Mean (SD) | 66.2 (7.44) | 63.3 (6.40) | 67.8 (10.0) | 66.1 (7.93) |
Median [Min, Max] | 66.0 [51.0, 85.0] | 63.0 [50.0, 77.0] | 68.0 [50.0, 89.0] | 66.0 [50.0, 89.0] |
Race | ||||
American Indian/Alaska Native | 2 (1.2%) | 1 (2.9%) | 0 (0%) | 3 (1.2%) |
Asian | 1 (0.6%) | 0 (0%) | 0 (0%) | 1 (0.4%) |
More Than One Race | 1 (0.6%) | 0 (0%) | 0 (0%) | 1 (0.4%) |
Unknown | 14 (8.5%) | 1 (2.9%) | 19 (41.3%) | 34 (13.9%) |
White | 147 (89.1%) | 32 (94.1%) | 27 (58.7%) | 206 (84.1%) |
Ethnicity | ||||
Hispanic or Latino | 7 (4.2%) | 0 (0%) | 3 (6.5%) | 10 (4.1%) |
Non-Hispanic or Latino | 127 (77.0%) | 29 (85.3%) | 24 (52.2%) | 180 (73.5%) |
Unknown | 31 (18.8%) | 5 (14.7%) | 19 (41.3%) | 55 (22.4%) |
CGG | ||||
Mean (SD) | 89.4 (18.6) | 77.5 (17.0) | 84.8 (18.4) | 86.9 (18.8) |
Median [Min, Max] | 87.0 [52.0, 183] | 76.0 [53.0, 135] | 83.0 [53.0, 130] | 84.0 [52.0, 183] |
Missing | 0 (0%) | 1 (2.9%) | 0 (0%) | 1 (0.4%) |
AGG Interruptions | ||||
0 | 83 (50.3%) | 20 (57.1%) | 19 (42.2%) | 122 (49.8%) |
1 | 50 (30.3%) | 11 (31.4%) | 15 (33.3%) | 76 (31.0%) |
2 | 32 (19.4%) | 4 (11.4%) | 11 (24.4%) | 47 (19.2%) |
APOε Genotype | ||||
ε2,ε2 | 3 (1.8%) | 0 (0%) | 0 (0%) | 3 (1.2%) |
ε2,ε3 | 17 (10.3%) | 5 (14.3%) | 3 (6.7%) | 25 (10.2%) |
ε2,ε4 | 5 (3.0%) | 0 (0%) | 1 (2.2%) | 6 (2.4%) |
ε3,ε3 | 111 (67.3%) | 24 (68.6%) | 28 (62.2%) | 163 (66.5%) |
ε3,ε4 | 29 (17.6%) | 6 (17.1%) | 12 (26.7%) | 47 (19.2%) |
ε4,ε4 | 0 (0%) | 0 (0%) | 1 (2.2%) | 1 (0.4%) |
KLOTHO Genotype | ||||
KL-VShet− | 110 (66.7%) | 25 (71.4%) | 31 (68.9%) | 166 (67.8%) |
KL-VShet+ | 50 (30.3%) | 10 (28.6%) | 9 (20.0%) | 69 (28.2%) |
KL-hom+ | 5 (3.0%) | 0 (0%) | 5 (11.1%) | 10 (4.1%) |
APOε4 Genotype | Comparison | Odds Ratio (95% CI) | p-Value |
No | (KL-VShet+ + or KL-VShom+) − (KL-VShet−) | 1.123 (0.612, 2.062) | 0.707 |
Yes | (KL-VShet+ + or KL-VShom+) − (KL-VShet−) | 1.63 (0.348, 7.644) | 0.535 |
KLOTHO Genotype | Comparison | Odds Ratio (95% CI) | p-Value |
KL-VShet− | APOε4 allele present—No APOε4 allele | 1.396 (0.644, 3.027) | 0.398 |
KL-VShet+ + or KL-VShom+ | APOε4 allele present—No APOε4 allele | 2.026 (0.46, 8.92) | 0.351 |
APOε4 Genotype | Comparison | Odds Ratio (95% CI) | p-Value |
No | (KL-VShet+ + or KL-VShom+) − (KL-VShet−) | 1.24 (0.616, 2.496) | 0.547 |
Yes | (KL-VShet+ + or KL-VShom+) − (KL-VShet−) | 1.077 (0.107, 10.854) | 0.950 |
KLOTHO Genotype | Comparison | Odds Ratio (95% CI) | p-Value |
KL-VShet− | APOε4 allele present—No APOε4 allele | 1.239 (0.502, 3.058) | 0.642 |
KL-VShet+ + or KL-VShom+ | APOε4 allele present—No APOε4 allele | 1.076 (0.112, 10.318) | 0.949 |
APOε4 | Comparison | Odds Ratio (95% CI) | p-Value |
No | APOε2 allele present—No APOε2 allele | 0.727 (0.311, 1.698) | 0.461 |
Yes | APOε2 allele present—No APOε2 allele | 0.758 (0.149, 3.855) | 0.738 |
APOε2 | Comparison | Odds Ratio (95% CI) | p-Value |
No | APOε4 allele present—No APOε4 allele | 1.477 (0.702, 3.105) | 0.304 |
Yes | APOε4 allele present—No APOε4 allele | 1.539 (0.288, 8.22) | 0.614 |
APOε4 | Comparison | Odds Ratio (95% CI) | p-Value |
No | APOε2 allele present—No APOε2 allele | 0.539 (0.218, 1.329) | 0.179 |
Yes | APOε2 allele present—No APOε2 allele | 0.61 (0.097, 3.822) | 0.597 |
APOε2 | Comparison | Odds Ratio (95% CI) | p-Value |
No | APOε4 allele present—No APOε4 allele | 1.142 (0.451, 2.891) | 0.779 |
Yes | APOε4 allele present—No APOε4 allele | 1.292 (0.206, 8.118) | 0.785 |
APOε4 | Comparison | Difference in Means (95% CI) | p-Value |
No | APOε2 allele present—No APOε2 allele | 8.4 (−11, 181) | 0.071 |
Yes | APOε2 allele present—No APOε2 allele | −4.6 (−181, 91) | 0.496 |
APOε2 | Comparison | Difference in Means (95% CI) | p-Value |
No | APOε4 allele present—No APOε4 allele | 3.7 (−51, 121) | 0.399 |
Yes | APOε4 allele present—No APOε4 allele | −9.3 (−231, 51) | 0.182 |
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Winarni, T.I.; Hwang, Y.H.; Rivera, S.M.; Hessl, D.; Durbin-Johnson, B.P.; Utari, A.; Hagerman, R.; Tassone, F. Apolipoproteine and KLOTHO Gene Variants Do Not Affect the Penetrance of Fragile X-Associated Tremor/Ataxia Syndrome. Int. J. Mol. Sci. 2024, 25, 8103. https://doi.org/10.3390/ijms25158103
Winarni TI, Hwang YH, Rivera SM, Hessl D, Durbin-Johnson BP, Utari A, Hagerman R, Tassone F. Apolipoproteine and KLOTHO Gene Variants Do Not Affect the Penetrance of Fragile X-Associated Tremor/Ataxia Syndrome. International Journal of Molecular Sciences. 2024; 25(15):8103. https://doi.org/10.3390/ijms25158103
Chicago/Turabian StyleWinarni, Tri Indah, Ye Hyun Hwang, Susan M. Rivera, David Hessl, Blythe P. Durbin-Johnson, Agustini Utari, Randi Hagerman, and Flora Tassone. 2024. "Apolipoproteine and KLOTHO Gene Variants Do Not Affect the Penetrance of Fragile X-Associated Tremor/Ataxia Syndrome" International Journal of Molecular Sciences 25, no. 15: 8103. https://doi.org/10.3390/ijms25158103
APA StyleWinarni, T. I., Hwang, Y. H., Rivera, S. M., Hessl, D., Durbin-Johnson, B. P., Utari, A., Hagerman, R., & Tassone, F. (2024). Apolipoproteine and KLOTHO Gene Variants Do Not Affect the Penetrance of Fragile X-Associated Tremor/Ataxia Syndrome. International Journal of Molecular Sciences, 25(15), 8103. https://doi.org/10.3390/ijms25158103