Elbow tendinopathy is a common pathology of the upper extremity that impacts both athletes and workers. Some research has examined the genetic component as a risk factor for tendinopathy, mainly in the lower limbs. A case-control study was designed to test for a relationship between certain collagen gene single nucleotide polymorphisms (SNPs) and elbow tendon pathology. A sample of 137 young adult athletes whose sports participation involves loading of the upper limb were examined for the presence of structural abnormalities indicative of pathology in the tendons of the lateral and medial elbow using ultrasound imaging and genotyped for the following SNPs: COL5A1 rs12722, COL11A1 rs3753841, COL11A1 rs1676486, and COL11A2 rs1799907. Anthropometric measurements and data on participants\' elbow pain and dysfunction were collected using the Disabilities of the Arm, Shoulder and Hand and the Mayo Clinic Performance Index for the Elbow questionnaires. Results showed that participants in the structural abnormality group had significantly higher scores in pain and dysfunction. A significant relationship between COL11A1 rs3753841 genotype and elbow tendon pathology was found (p = 0.024), with the CT variant associated with increased risk of pathology.

OBJECTIVE: To examine the impact of demographic, clinical, and genetic factors as well as herniated discs on 5-year development of disc degeneration in the lumbar spine, and to investigate associations between changes in lumbar degenerative findings and pain.
METHODS: In 144 patients with lumbar radicular pain or low back pain, we scored disc degeneration, herniated discs, and high-intensity zones in the posterior annulus fibrosus on lumbar magnetic resonance imaging (MRI) at baseline and 5-year follow-up. Genotyping (TaqMan assay) was performed for genes encoding vitamin D receptor (VDR), collagen XIα (COL11A), matrix metalloproteinase 1/9 (MMP1/MMP9), and interleukin 1α/1RN (IL-1α/IL-1RN). Associations were analyzed using multivariate linear regression adjusted for age, sex, smoking, body mass index, and baseline scores for degenerated discs and herniated discs (when analyzing impact of baseline factors) or for pain (when analyzing associations with pain).
RESULTS: Progression of disc degeneration over 5 years was significantly (p < 0.001) related to higher age and less disc degeneration at baseline, but not to sex, smoking, body mass index, herniated discs, or variants in the studied genes. No associations were identified between changes in disc degeneration or high-intensity zones and pain at 5-year follow-up. However, increased number of herniated discs over 5 years was associated with pain at rest (p = 0.019).
CONCLUSIONS: Age and disc degeneration at baseline, rather than genetic factors, influenced the 5-year development of disc degeneration in patients with lumbar radicular pain or low back pain. Development of herniated discs was related to pain at rest.

OBJECTIVE: To evaluate the association between high myopia (HM) and single nucleotide polymorphisms (SNPs) in collagen, type XI, alpha 1 (COL11A1) and collagen, type XVIII, alpha 1 (COL18A1) genes in a Han Chinese population.
METHODS: A total of 869 patients with HM and 804 controls were recruited for this study. The genotyping of five SNPs in COL11A1 and COL18A1 was performed using the SNaPshot method. The genotyping data were analyzed using the χ2 test, and the linkage disequilibrium block structure was calculated and examined by Haploview software.
RESULTS: No statistically significant differences (p > 0.05) were identified between HM cases and controls after a Bonferroni correction for multiple tests in the allele frequencies of COL11A1 and COL18A1 SNPs. However, the G allele of rs2236475 showed a susceptible effect for HM (p = 0.016, corrected p = 0.08, odds ratio [OR] = 1.26). Moreover, the carriers of rs2236475GG genotype displayed an increased risk of HM compared with the rs2236475AA and rs2236475AG+AA genotypes (p = 0.008, OR = 1.79, confidence interval [95% CI] = 1.18-2.64, uncorrected; p = 0.012, OR = 1.74, 95% CI = 1.12-2.57, corrected, respectively).
CONCLUSIONS: Our results suggested that common polymorphisms in these two candidate genes were unlikely to play major roles in the genetic susceptibility to HM. Nevertheless, to avoid filtering real myopia genes, the role of COL11A1 and COL18A1 in the pathogenesis of myopia requires more refinement in both animal models and human genetic epidemiological studies.

A previous study identified a significant association between several single nucleotide polymorphisms (SNPs) and lumbar disc degeneration (LDD) in Indians. To validate the association between these SNPs and specific lumbar spine pathologies, we performed a case-control study in Chinese Han population.
An observational study.
University Hospital in Nanning, China.
This study included 428 patients with LDD and 400 normal controls.
Patients with LDD were classified into four subgroups, including disc herniation only (subgroup 1), discopathies or/and osteochondrosis associated with disc herniation (subgroup 2), spinal stenosis or/and spondylolisthesis (subgroup 3) and degenerative scoliosis (subgroup 4). This study was conducted by examining two aspects: environmental factors and SNP genotyping. The environmental factors were evaluated with a questionnaire survey including questions about body mass index, smoking habits, the physical demands of their job and exposure to vibrations. Rs1337185, rs5275, rs5277, rs7575934, rs3213718 and rs162509 were genotyped using a PCR-based invader assay.
The physical workload was significantly higher in patients with lumbar spine pathologies than in the normal controls (p=0.035). The genotype and allele frequencies of rs1337185 and rs162509 were significantly different between the patients with LDD and the normal controls. In rs1337185, a significant association was found between the C allele (risk allele) and the presence of disc herniation (OR=1.80; 95% CI 1.21 to 2.68; p=0.003, adjusted p=0.012) and the presence of spinal stenosis and spondylolisthesis (OR=1.92; 95% CI 1.29 to 2.89; p=0.001, adjusted p=0.004). In rs162509, the G allele represented 1.58-fold increased risk to suffer from disc herniation (OR=1.58; 95% CI 1.20 to 2.09; p=0.001, adjusted p=0.004).
The SNPs rs1337185 in COL11A1 and rs162509 in ADAMTS5 are associated with susceptibility to LDD. The C allele of rs1337185 is risky for patients who are affected by lumbar pathologies such as disc herniation, stenosis and spondylolisthesis. The G allele of rs16250 represents a risk factor for the development of disc herniation.

Patients with Cushing\'s Syndrome (CS) in remission were used as a model to test the hypothesis that long-standing excessive cortisol exposure induces changes in DNA methylation that are associated with persisting neuropsychological consequences. Genome-wide DNA methylation was assessed in 48 women with CS in long-term remission (cases) and 16 controls matched for age, gender and education. The Fatigue impact scale and the comprehensive psychopathological rating scale were used to evaluate fatigue, depression and anxiety. Cases had lower average global DNA methylation than controls (81.2% vs 82.7%; p = 0.002). Four hundred and sixty-one differentially methylated regions, containing 3,246 probes mapping to 337 genes were identified. After adjustment for age and smoking, 731 probes in 236 genes were associated with psychopathology (fatigue, depression and/or anxiety). Twenty-four gene ontology terms were associated with psychopathology; terms related to retinoic acid receptor signalling were the most common (adjusted p = 0.0007). One gene in particular, COL11A2, was associated with fatigue following a false discovery rate correction. Our findings indicate that hypomethylation of FKBP5 and retinoic acid receptor related genes serve a potential mechanistic explanation for long-lasting GC-induced psychopathology.

The Stickler syndrome (SS) has been described as a \"hereditary progressive arthro-ophtalmopathy\" by Stickler in 1965, due to mutations on the collagen genes. Currently about 40 different genes have been identified which encode for at least 27 different collagens. The majority of mutations occur in the COL2A1 gene on chromosome 12q13 (SS type I). Mutations in COL11A1 are less frequent (SS type II). More recently, mutations in COL11A2 and in the COL9A1 gene have been reported with particular phenotypes. The main features of this autosomal inherited disease are ocular, auditory with orofacial abnormalities and early-onset osteoarthritis. We report the clinical presentation of an adult and his son, with a particular focus on the bone status of the father, radiography, bone densitometry and transiliac bone biopsy showing that he was suffering from osteoporosis. The lumbar bone mineral density was low with a Z-score at -2.9. Transiliac bone biopsy showed a dramatic decrease of trabecular bone volume (8.6%; Nl: 19.5±4.9%), thin trabeculae and a disorganized trabecular network. A slight increase of osteoid parameters was observed. Bone resorption was markedly increased with an excessive number of active (TRAcP+) osteoclasts. The cortical width was normal, but a slight increase of cortical porosity was found. Osteoporosis has been rarely described in the SS. It might be useful to systematically perform a bone densitometry in all patients with SS and to discuss the indication of a transiliac bone biopsy in severe cases.

OBJECTIVE: To investigate the association of PLEKHA7 and COL11A1 with primary angle closure glaucoma, as well as acute and chronic subphenotype, in a Han Chinese population.
METHODS: A total of 984 cases, including 606 primary angle closure glaucoma (PACG) and 378 primary angle closure (PAC), and 922 normal controls were recruited. Twelve single nucleotide polymorphisms (SNPs) (rs1676486, rs3753841, rs12138977, rs2126642, rs2622848, rs216489, rs1027617, rs366590, rs11024060, rs6486330, rs11024097, and rs11024102) in the PLEKHA7 gene and COL11A12 gene were genotyped. Distributions of allele frequencies were compared between cases and controls as well as in patient subgroups with or without acute attacks.
RESULTS: Four of the 12 SNPs, including rs1676486 (P = 0.0060) and rs12138977 (P = 0.028) in COL11A1, as well as rs216489 (P = 0.0074) and rs11024102 (P = 0.038) in PLEKHA7, were found to have a statistically significant association with PAC/PACG. In the subgroup analysis, 6 out of 12 SNPs (rs1676486, rs3753841, rs12138977, rs216489, rs11024060, and rs11024102) showed statistically significant differences between acute PAC/PACG cases and controls. However, none of them showed statistically significant differences between chronic PAC/PACG cases and controls.
CONCLUSIONS: Our study suggests that rs1676486 and rs12138977 in COL11A1 as well as rs216489 and rs11024102 in PLEKHA7 are associated with an increased risk of PAC/PACG in the Han Chinese population, supporting prior reports of the association of COL11A1 and PLEKH7 with angle closure glaucoma. Both COL11A1 and PLEKHA7 were shown to confer significant risk for acute PAC/PACG. Further work is necessary to confirm the importance of COL11A1 and PLEKHA7 in the pathogenesis of glaucoma.

OBJECTIVE: Three loci defined by single nucleotide polymorphisms (SNPs) rs11024102 in PLEKHA7, rs3753841 in COL11A1, and rs1015213 between the PCMTD1 and ST18 genes, recently have been associated with primary angle closure glaucoma (PACG). We explored the genetic association of these SNPs with subtypes of primary angle closure in a South Indian population.
METHODS: The study included three case definitions: primary angle closure/primary angle closure glaucoma (PAC/PACG, N = 180); primary angle closure suspect (PACS, N = 171), and a combined any-angle closure group. Controls consisted of 411 individuals from South India. Genotyping for all three SNPs was performed using the TaqMan allelic discrimination assay. Genetic association was estimated using a χ(2) test statistics and logistic regression.
RESULTS: Among the three studied SNPs, significant genetic association was identified for rs1015213 in the PAC/PACG (P = 0.002) and any-angle closure (P = 0.003) analyses. However, no significant genetic association was seen when in PACS subjects (P = 0.052). SNPs rs3753841 and rs11024102 showed no evidence of genetic association with angle-closure phenotypes (P > 0.05) in South Indian participants.
CONCLUSIONS: In our study, rs1015213 (located in the intergenic region between PCMTD1 and ST18) was associated significantly with PAC/PACG, confirming prior reports of an association between this region and angle closure glaucoma. Further work with a larger sample size is necessary to confirm the importance of COL11A1 and PLEKHA7 in the pathogenesis of glaucoma.

OBJECTIVE: To investigate if the single nucleotide polymorphisms rs3753841, rs1015213 and rs11024102, recently implicated in the development of acute primary angle closure or primary angle closure glaucoma, are associated with ocular biometric characteristics of British adults in the European Prospective Investigation of Cancer-Norfolk eye study.
METHODS: Genotyping data on rs1015213 (between PCMTD1 and ST18), rs11024102 (at PLEKHA7) and rs3753841 (at COL11A1) were available on 3268 participants. Direct genotypic data was available for rs1015213 and rs3753841. Data was imputed for rs11024102. Ocular biometric data was available on 1137 participants who attended the third European Prospective Investigation of Cancer health examination and 988 (87%) of these participants had no previous cataract surgery either eye. Axial length (AL), anterior chamber depth (ACD) and corneal keratometry were measured by using the Zeiss IOLMaster.
RESULTS: Presence of at least one A allele (AG or AA genotype) for rs1015213 was associated with a shallower ACD (-0.07 mm, 95% CI -0.01 to -0.14 mm, p=0.028) after adjusting for age and sex (both p≤0.001). There was no association with AL or corneal keratometry for rs1015213 genotypes. AL, ACD and keratometry were not associated with rs3753841 or rs11024102 genotypes including after adjusting for age and sex.
CONCLUSIONS: This study suggests that primary angle closure glaucoma susceptibility at the PCMTD1-ST18 locus may be partly explained by an association between rs1015213 and ACD in European populations. This effect is equivalent to almost 20% of the SD of the mean ACD of phakic individuals in this cohort. We were not able to identify any association between rs3753841 or rs11024102 and ocular biometry.

OBJECTIVE: We examined the relationship between high myopia and common polymorphisms in four candidate genes: collagen, type XI, alpha 1 (COL11A1); collagen, type XVIII, alpha 1 (COL18A1); fibrillin 1 (FBN1); and procollagen-lysine 1,2-oxoglutarate 5-dioxygenase 1 (PLOD1). These genes were selected because rare pathogenic mutations in these genes cause disease syndromes that have myopia, usually high myopia, as one of the common presenting features.
METHODS: This study recruited 600 unrelated Han Chinese subjects including 300 cases with high myopia (spherical equivalent or SE≤-8.00 diopters) and 300 controls (SE within ±1.00 diopter). A total of 66 tag single nucleotide polymorphisms (SNPs) were selected for study from these four candidate genes. The study adopted a DNA pooling strategy with an initial screen of DNA pools to identify putatively positive SNPs and then confirmed the \"positive\" SNPs by genotyping individual samples forming the original DNA pools. DNA pools were each constructed by mixing equal amounts of DNA from 50 individuals with the same phenotype status. Six case pools were prepared from 300 cases and six control pools from 300 controls. Allele frequencies of DNA pools were estimated by analyzing the primer-extended products with denaturing high performance liquid chromatography and compared between case pools and control pools with nested ANOVA.
RESULTS: In the first stage, 60 SNPs from the 4 candidate genes were successfully screened using the DNA pooling approach. Of these, 6 SNPs showed a statistical significant difference in estimated allele frequencies between case pools and controls at p<0.10. In the second stage, these \"positive\" SNPs were followed up by individual genotyping, but failed to be confirmed via standard single-marker and haplotype analyses.
CONCLUSIONS: Common polymorphisms in these four candidate genes (COL11A1, COL18A1, FBN1 and PLOD1) were unlikely to play important roles in the genetic susceptibility to high myopia.