The gene-work exposure interaction in causing intervertebral disc (HIVD) in Taiwa n

1. The gene-work exposure interaction in causingintervertebral disc (HIVD) in Taiwan Hung YJ1, Shih TTF2, Chen BB2, Hung CH1, Ma LP1, Hwang YH1, Yang SH3, Hsu HC3, Wang TM3, Liou SH45, Guo YL6 1Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, Taiwan 2Department of Medical Imaging and Radiology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taiwan 3Department of Orthopaedic Surgery, National Taiwan University Hospital Taiwan 4Department of Public Health, National Defense Medical Center, Taiwan 5DEHOM, National Health research Institute, Taiwan 6Department of Environmental and Occupational Medicine, National Taiwan University, Taiwan Background Result Herniated intervertebral disc (HIVD) is listed as an occupational disease in Taiwan’s workers’ compensation system. It was also of high prevalence and cost in developed countries. Heavy lifting is one of known occupational risk factors. Nevertheless, the quantification of the aforementioned exposure has been controversial and the dose-response relationship with the disease has not been established. Therefore, we conducted a hospital-based case-control study to examine the dose-response relationship with HIVD. In the hospital-based case-control study, 250 subjects were invited to the study. Total of 91 cases and 91 controls were entered for the final analysis. HIVD are associated with longer working tenure, higher education level, daily smoking and exercise (Table 1). Life time cumulative load in L4-5 due to lifting, were higher in HIVD cases as compared to the controls. (Table 2). While categorized into three groups, the highest cumulative lift load group had increased odds ratio of 2.6 (95% confidence interval 1.2-5.5). The p value for trend was 0.013. While categorized into two groups, the higher cumulative lift load group had increased odds ratio of 1.1 (95% confidence interval 1.1-3.5). After adjusted for BMI, the odds ratio (OR) for highest lift load was 2.5 (95% CI 1.2 to 5.4) . The result of the study suggested life time cumulated lift load is associated with HIVD, showing a dose-response gradient. While adjusting for BMI, highest lifting was associated with HIVD. Among the highly lifting group, those with CT/TT genotypes of VDR gene had higher risk than those with CC genotypes (Table 4). THBS2 gene with AA/GA genotypes in high lifting group had had borderline increased odds ratio of 1.9 than those with GG genotype (Table 5). In addition, those with MMP9 carrying the G allele have higher risk than those without G allele (Table 6). Method For the hospital based case-control study, the inclusion criteria were (1) patients aged 20-65 years of age, (2) with diagnosed HIVD of lumbar spine L3-4, L4-5, and/or L5-S1 from the Orthopedics clinic in the National Taiwan University Hospital. The determinants of HIVD in this study are protruding or extruding or sequestrated disc confirmed by Magnetic Resonance Imaging (MRI). Controls were recruited from patients visiting the Internal Medicine clinic of the same hospital for upper respiratory infection, with the same gender, similar age (within 5 years), and aged between 20-65 years. The controls were excluded from the analysis if they were found to have HIVD in any of the lumbar to sacral intervertebral discs. The participants were assessed with questionnaire for demographics, leisure activities, and detailed work experience especially on weight lifting, MRI of the L-S spine, and blood testing. They were asked to describe and perform working posture for each job description that lasted for 6 months or longer in their lifetime. The compression force on lumbar 4-5 disc in lifting, standing and sitting were estimated later by using the 3-dimention Static Strength Prediction Program (3D SSPP) software system. PCR and Sequencing technique were performed to analysis the DNA for COL9A2 and VDR Taq 1, VDR Fok 1, THBS2 and MMP9 genotype variations. Conclusion In conclusion, we examined the interaction of weight lifting at work and genotypic polymorphisms on causing HIVD. Cumulative lift load was associated with risk of HIVD. VDR with TT/TC genotypes and MMP9 with GG/GA seemed to interact with lift load and played susceptibility factor among workers exposed to weight-lifting. Continuous recruitment of participants will allow for better statistical power in answering the important research question of gene-environment interaction in causing HIVD in workers. Acknowledgement This study was supported by grants NHRI-97A1-PDCO-01-0811-1 from National Health research Institute , Taiwan, ROC.