PlA2 Polymorphism of Platelet Glycoprotein IIb/IIIa and C677T Polymorphism of Methylenetetrahydrofolate Reductase (MTHFR), but Not Factor V Leiden and Prothrombin G20210A Polymorphisms, Are Associated with More Severe Forms of Legg–Calvé–Perthes Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Controls
2.3. Genetic Analysis
2.4. Risk Haplotypes
2.5. Catterall Stages Classification of Severity
2.6. Statistical Analysis
3. Results
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- PlA2 polymorphism of the platelet membrane glycoprotein (GP) IIb/IIIa (rs5918(C)). Similar distributions in both LCPD cases and controls were observed for alleles and genotypes; thus, no significant risk for LCPD can be attributed to the presence of this polymorphism. The prevalence of mutated alleles was 17.1% (95% confidence intervals 10.5 to 26.6) in LCPD patients and 14.4% (95% confidence intervals, 10.5 to 19.5) in controls. The odds ratio of the A2 allele versus the A1 allele was 1.22 (95% confidence intervals 0.6 to 2.4; p = 0.561). The odds ratio for LCPD in those who were homozygous or heterozygous for the mutated allele relative to subjects with a normal genotype was 1.3 (95% confidence intervals 0.6 to 2.8).
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- Mutation C677T of metilenetetrahydrofolate reductase (MTHFR), (rs1801133(T)). No significant differences in allele frequencies were detected between cases of LCPD and controls. The prevalence of mutated alleles was 32.9% (95% confidence intervals 23.7 to 43.6) in the group of LCPD hips and 36% (confidence intervals 95% 30.2 to 42.3) in the controls, with the odds ratio of T versus C being 0.9 (95% confidence intervals 0.4 to 1.4).
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- Factor V Leiden mutation in the F5 gene causing factor V Leiden thrombophilia (rs6025(A)). Most cases (97%) and controls (99%) had a normal genotype for G1691A mutation in the F5 gene. No cases of mutated homozygous haplotypes were identified, either in cases or in controls. However, a positive trend was observed between LCPD and the presence of factor V Leiden mutation, with the odds ratio of A versus G being 2.9 (95% confidence intervals of 0.2 to 46.9).
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- G20210A mutation of the prothrombin F2 gene (rs1799963(A)). All patients with LCPD and most of the controls (97%) were G/G homozygous for the G20210A mutation of prothrombin F2 gene, and only four of the controls were heterozygous (G/A) for the polymorphism. No homozygous AA cases were detected. The prevalence of mutated A alleles was 1.7% (95% confidence intervals 0.6 to 4.3) in the controls, whereas no mutated A alleles were detected in the cases, with an odds ratio of 0.3 (95% confidence intervals 0.01 to 5.7) for allele A with respect to the G allele.
Genetic Haplotypes
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Genotypes/Alleles | Controls | LCPD | OR (CI95%) | p | |
---|---|---|---|---|---|
Factor V | GG | 117 (99.2%) | 49 (96.1%) | 1 | 0.206 |
GA | 1 (0.8%) | 2 (3.9%) | 4.8 (0.4 to 53.9) | ||
AA | 0 | 0 | |||
Allele frequencies | G | 235 (99%) | 100 (98%) | 0.452 | |
A | 1 (1%) | 2 (2%) | 4.7 (0.4 to 52.4) | ||
MTHFR | CC | 47 (39.8%) | 26 (51%) | 1 | 0.181 |
CT | 57 (48.3%) | 20 (39.2%) | 0.6 (0.3 to 1.2) | ||
TT | 14 (11.9%) | 5 (9.8%) | |||
Allele frequencies | C | 151 (63.9%) | 72 (70.6%) | 0.290 | |
T | 85 (36.1%) | 30 (29.4%) | 0.7 (0.4 to 1.2) | ||
GP IIb/IIIa | A1A1 | 87 (73.7%) | 34 (66.7%) | 1 | |
A1A2 | 28 (23.7%) | 16 (31.4%) | 1.4 (0.7 to 2.9) | 0.351 | |
A2A2 | 3 (2.5%) | 1 (1.9%) | |||
Allele frequencies | A1 | 202 (85.6%) | 84 (82.4%) | ||
A2 | 34 (14.4%) | 18 (17.6%) | 1.4 (0.7 to 2.4) | 0.552 | |
Prothrombin | GG | 114 (96.6%) | 51 (100%) | 1 | |
GA | 4 (3.4%) | 0 (0%) | 0.000 | 0.999 | |
AA | 0 (0%) | 0 (0%) | |||
Allele frequencies | G | 232 (98.3%) | 102 (100%) | ||
A | 4 (1.7%) | 0 | 0.3 (0.01 to 4.7) | 0.438 |
Number of Evaluated LCPD Hips = 51 | |||||
---|---|---|---|---|---|
Low Risk * n = 31 | Intermediate Risk * n = 14 | High Risk * n = 6 | |||
A1A1–CC | 15 (48.4%) | A1A2–CT | 3 (21.4%) | A2A2–TT | 0 |
A1A1–CT | 16 (51.6%) | A1A2–CC | 11 (78.6%) | A1A2–TT | 2 (33.3%) |
A1A1–TT | 3 (50%) | ||||
A2A2–CT | 1 (16.7%) | ||||
A2A2–CC | 0 |
Haplotypes | ||||
---|---|---|---|---|
Low Risk * | Intermediate Risk * | High Risk * | p | |
Catterall I | 1 (3.2%) | 1 (7.1%) | 1 (16.7%) | 0.05 |
Catterall II | 2 (6.5%) | 5 (35.7%) | 0 | |
Catterall III | 16 (51.6%) | 4 (28.6%) | 1 (16.7%) | |
Catterall IV | 12 (38.7%) | 4 (28.6%) | 4 (66.6%) |
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García-Alfaro, M.D.; Pérez-Nuñez, M.I.; Amigo, M.T.; Arbona, C.; Ballesteros, M.Á.; González-Lamuño, D. PlA2 Polymorphism of Platelet Glycoprotein IIb/IIIa and C677T Polymorphism of Methylenetetrahydrofolate Reductase (MTHFR), but Not Factor V Leiden and Prothrombin G20210A Polymorphisms, Are Associated with More Severe Forms of Legg–Calvé–Perthes Disease. Children 2021, 8, 614. https://doi.org/10.3390/children8070614
García-Alfaro MD, Pérez-Nuñez MI, Amigo MT, Arbona C, Ballesteros MÁ, González-Lamuño D. PlA2 Polymorphism of Platelet Glycoprotein IIb/IIIa and C677T Polymorphism of Methylenetetrahydrofolate Reductase (MTHFR), but Not Factor V Leiden and Prothrombin G20210A Polymorphisms, Are Associated with More Severe Forms of Legg–Calvé–Perthes Disease. Children. 2021; 8(7):614. https://doi.org/10.3390/children8070614
Chicago/Turabian StyleGarcía-Alfaro, María Dolores, María Isabel Pérez-Nuñez, María Teresa Amigo, Carmelo Arbona, María Ángeles Ballesteros, and Domingo González-Lamuño. 2021. "PlA2 Polymorphism of Platelet Glycoprotein IIb/IIIa and C677T Polymorphism of Methylenetetrahydrofolate Reductase (MTHFR), but Not Factor V Leiden and Prothrombin G20210A Polymorphisms, Are Associated with More Severe Forms of Legg–Calvé–Perthes Disease" Children 8, no. 7: 614. https://doi.org/10.3390/children8070614