RESUMEN
A recent genetic association study has revealed that a variant (rs143383) within the 5'-untranslated region of the growth differentiation factor 5 gene (GDF5) associates with the risk of Achilles tendon pathology. The aim of this study was to determine whether this variant associates with the risk of ACL rupture. A cohort of 126 Caucasians with ACL rupture (ACL group), including 51 subjects who ruptured their ACL through a non-contact mechanism (NON sub-group), and 214 controls (CON group) were genotyped for the rs143383 variant. We report no significant GDF5 rs143383 genotype (P=0.396) or allele (P=0.810) frequency differences between the ACL (TT genotype, n=37, 29%; CT genotype, n=72, 57%; CC genotype, n=17, 14%) and CON (TT genotype, n=73, 34%; CT genotype, n=106, 50%; CC genotype, n=35, 16%) groups. There were also no significant differences between the NON sub-group and the CON group (allele; P=0.710, genotype; P=0.771). Furthermore, in gender specific analysis we found no association between rs143383 and ACL in either males (allele; P=0.988, genotype; P=0.407) or females (allele; P=0.643, genotype; P=0.885), respectively. Nor were there any gender specific associations between the NON sub-group and either genotype or allele. In conclusion, the rs143383 variant was not found to associate with the risk of ACL rupture.
Asunto(s)
Regiones no Traducidas 5'/genética , Lesiones del Ligamento Cruzado Anterior , Factor 5 de Diferenciación de Crecimiento/genética , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Rotura/genéticaRESUMEN
As matrix metalloproteinases (MMPs) are critical to ligament homeostasis and integrity, the aim of this study was to investigate whether four functional polymorphisms within four MMP genes, which cluster on chromosome 11q22 associate with risk of ACL ruptures. Three hundred and forty-five [129 with ACL ruptures (ACL group) and 216 asymptomatic controls (CON group)] unrelated Caucasians were recruited for this case-control study. Fifty-four participants reported non-contact mechanisms of ACL rupture (NON subgroup). All participants were genotyped for the MMP10 C/T rs486055, MMP1 1G/2G rs1799750, MMP3 G/A rs679620 and MMP12 A/G rs2276109 variants. After adjusting for sex, age and weight, the AG and GG genotypes of the MMP12 rs2276109 variant were significantly (P=0.030) under-represented among the NON subgroup (14%), when compared with the CON group (26%). No other variants were significantly different between groups. Adjusted for the same confounders, the two four-variant haplotypes T-1G-A-A (CON 14%, ACL 9%, P=0.033) and C-2G-G-G (CON 14%, NON 5%, P=0.021) were significantly different between the CON and the ACL groups, and the CON group and the NON subgroup, respectively. This is the first report that indicates an association between the chromosomal region 11q22 and the risk of ACL rupture.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Cromosomas Humanos Par 11/genética , Traumatismos de la Rodilla/genética , Metaloproteinasas de la Matriz/genética , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 10 de la Matriz/genética , Metaloproteinasa 12 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/genética , Polimorfismo de Nucleótido Simple , Rotura/genética , Adulto JovenRESUMEN
BACKGROUND: Anterior cruciate ligament (ACL) ruptures are considered the most severe injury sustained in sports. Although various intrinsic and extrinsic risk factors have been identified, the exact aetiology of the injury is not yet fully understood. Recently, the gene encoding for the alpha1 chain of type I collagen (COL1A1) has been shown to be associated with cruciate ligament ruptures and shoulder dislocations. OBJECTIVE: To determine whether the functional Sp1 binding site polymorphism within intron 1 of the COL1A1 gene is associated specifically with ACL ruptures in an independent population. METHODS: 117 Caucasian participants with surgically diagnosed ACL ruptures, and 130 Caucasian physically active controls without any history of previous ligament or tendon injuries were recruited for this case-control genetic association study. All participants were genotyped for the COL1A1 Sp1 binding site polymorphism (G/T; rs1800012). RESULTS: The rare TT genotype was significantly (p = 0.031, OR = 0.08, 95% CI <0.01 to 1.46) under-represented in the ACL group (0 out of 117, 0%), compared with the controls (6 out of 130, 4.6%). CONCLUSION: The TT genotype of the COL1A1 Sp1 binding site polymorphism was significantly under-represented in South African participants with ACL ruptures. We propose that this sequence variant be the first specific genetic element to be included in multifactorial models developed to understand the aetiology and risk factors for ACL rupture.