COL1A1 and COL2A1 genes and myopia susceptibility: evidence of association and suggestive linkage to the COL2A1 locus

PURPOSE. Collagen involvement in myopia development via scleral remodeling is well-known. Recently, COL1A1 and COL2A1 gene polymorphisms were reported to be associated with high-grade and common myopia, respectively. This study was conducted to investigate whether these collagen genes are associated and/or genetically linked with myopia in large Caucasian family datasets. METHODS. High-grade myopia was defined as ??5.00 D. Two independent datasets comprising 146 (Duke) and 130 (Cardiff) families with high-grade myopia participated in the association study. Allelic discrimination assays were performed on tagging SNPs for COL1A1 and COL2A1. The pedigree disequilibrium test (PDT) and the association test in the presence of linkage (APL) were used for association analyses. Linkage analyses for COL2A1 locus markers were performed with the Fastlink and Merlin programs in conjunction with data obtained from our collaborative whole-genome linkage study (254 families). RESULTS. Significant association was identified between five SNPs (rs1034762, rs1635529, rs1793933, rs3803183, and rs17122571) of the COL2A1 locus and high-grade myopia (P ? 0.045, minimum (min) P ? 0.008) and with myopia status set at ??0.50 or ?0.75 D (min P ? 0.004) in the Duke dataset. The SNP rs1635529 also showed significant association in the Cardiff dataset (??5.00 D, min P ? 0.004; ??0.50 D, min P ? 0.007). Linkage analyses showed suggestive linkage to the COL2A1 locus on 12q. No association was found between COL1A1 SNPs and any degree of myopia. CONCLUSIONS. The COL2A1 gene was associated with highgrade myopia in two independent Caucasian family datasets. COL1A1 gene polymorphisms were not associated with myopia in our dataset, indicating possible heterogeneity across different ethnicities

Development and description of measurement properties of an instrument to assess treatment burden among patients with multiple chronic conditions

<p>Abstract</p> <p>Background</p> <p>Patients experience an increasing treatment burden related to everything they do to take care of their health: visits to the doctor, medical tests, treatment management and lifestyle changes. This treatment burden could affect treatment adherence, quality of life and outcomes. We aimed to develop and validate an instrument for measuring treatment burden for patients with multiple chronic conditions.</p> <p>Methods</p> <p>Items were derived from a literature review and qualitative semistructured interviews with patients. The instrument was then validated in a sample of patients with chronic conditions recruited in hospitals and general practitioner clinics in France. Factor analysis was used to examine the questionnaire structure. Construct validity was studied by the relationships between the instrument's global score, the Treatment Satisfaction Questionnaire for Medication (TSQM) scores and the complexity of treatment as assessed by patients and physicians. Agreement between patients and physicians was appraised. Reliability was determined by a test-retest method.</p> <p>Results</p> <p>A sample of 502 patients completed the Treatment Burden Questionnaire (TBQ), which consisted of 7 items (2 of which had 4 subitems) defined after 22 interviews with patients. The questionnaire showed a unidimensional structure. The Cronbach's α was 0.89. The instrument's global score was negatively correlated with TSQM scores (r_s= -0.41 to -0.53) and positively correlated with the complexity of treatment (r_s= 0.16 to 0.40). Agreement between patients and physicians (n = 396) was weak (intraclass correlation coefficient 0.38 (95% confidence interval 0.29 to 0.47)). Reliability of the retest (n = 211 patients) was 0.76 (0.67 to 0.83).</p> <p>Conclusions</p> <p>This study provides the first valid and reliable instrument assessing the treatment burden for patients across any disease or treatment context. This instrument could help in the development of treatment strategies that are both efficient and acceptable for patients.</p