Gamma-glutamyl-transferase is associated with incident hip fractures in women and men ≥ 50 years: a large population-based cohort study.

The association of serum gamma-glutamyl-transferase (GGT) with hip fracture risk has not been examined in women and men ≥ 50 years. We show that elevated GGT was associated with increased hip fracture risk, particularly in men. GGT could be a candidate serum marker of long-term hip fracture risk in the elderly. INTRODUCTION: We herein examined a possible relation between serum levels of GGT and hip fracture risk in women and men aged ≥ 50 years, which has not been investigated before. METHODS: In this population-based prospective cohort study, approximately 41,000 women and nearly 33,000 men ≥ 50 years participating in a medical prevention program 1985-2005 in western Austria were followed up for the occurrence of osteoporotic hip fractures during 2003-2013. ICD-10 based discharge diagnoses for hip fracture included S72.0, S72.1, and S72.2 available from all regional hospitals. GGT-related hip fracture risk was ascertained at each participant´s first and last examination during the prevention program. In a subset of 5445 participants, alcohol consumption could be included as a covariate. RESULTS: In men, hip fracture risk rose significantly by 75% and 86% for every tenfold increase of GGT measured at the first and last examination, respectively, and in women, hip fracture risk rose by 22% from the last examination. Elevated GGT (≥ 36 U/l in women, ≥ 56 U/l in men) at the first examination was associated with increased hip fracture risk only in men (HR 1.51, 95% CI 1.25-1.82), and at the last examination in both women (HR 1.14, 95% CI 1.02-1.28) and men (HR 1.61, 95% CI 1.33-1.95). Alcohol consumption had no significant influence on GGT-mediated hip fracture risk in women and men. CONCLUSIONS: Our findings identified an association of elevated GGT and hip fracture in women and men ≥ 50 years and suggest GGT as a candidate serum marker of long-term hip fracture risk in an elderly population.

Accurate quantitation of JAK2 V617F allele burden by array-based digital PCR.

INTRODUCTION: The JAK2 V617F mutation is highly prevalent in patients with myeloproliferative neoplasms (MPN). Several studies have shown that allele burden correlates with hematologic characteristics and clinical end-points in patients with MPN. Allele-specific real-time quantitative polymerase chain reaction (RQ-PCR) is probably the most commonly used technique for detection and quantitation of the JAK2 V617F mutation. Alternatively, digital PCR is an emerging technology for absolute DNA quantitation, which is based on dilution and high-grade partitioning of a sample. METHODS: We compared array-based digital PCR using the QuantStudio(™) 3D Digital PCR System platform with a RQ-PCR assay, CE-registered for in vitro diagnostic use, regarding JAK2 V617F allele quantitation. This study included 30 samples positive for the JAK2 V617F mutation and additionally 13 samples without the mutation. RESULTS: JAK2 V617F allele burden of samples ranged between well below 1% and more than 90%. Linear regression analysis showed a high correlation between the results obtained from the two techniques (r(2) = 0.9983). Thirteen samples tested negatively for the JAK2 V617F mutation with RQ-PCR were also found negative with digital PCR. CONCLUSION: We conclude that array-based digital PCR is an appropriate method for the quantitation of JAK2 V617F allele burden demonstrating highest correlation with allele-specific RQ-PCR.