| BackgroundLumbar degenerative disc disease (LDDD) is a common disease affecting a large portion of the whole population. It places great burden to our society. It is well accepted that LDDD is a multifactorial disease, caused by both environment and genetic factors. However, the exact modes of action of its genetic risk factors are still unknown. Previous studies showed that the breakdown of proteoglycans (PG) and glycosaminoglycans (GAG) are the earliest events of the pathogenesis of LDDD. A disintegrin and metallop roteinase with thrombospondin motifs (ADAMTS) is the mojor enzyme responsible for the degradation of PGs and GAGs. Our study examines the environment factors and the Single Nucleotide Polymorphism (SNP) of ADAMTS-4gene between LDDD case group and control group.Objects1. To study the environment risk factors of Northern Chinese Han population.2. To identify the association between ADAMTS-4polymorphisms and LDDD in Northern Chinese Han population.3. Through MRI imaging, to study the relationship between ADAMTS polymorphism and disc degeneration.4. To illustrate the combined effects of environment factors and ADAMTS polymorphism on LDDD in Northern Chinese Han people.MethodsA case control study is used to investigate the association between environment factors, ADAMTS-4polymorphisms and LDDD in Northern Chinese Han people.Results1. Among potential environment risk factors investigated, the positive family history of LDDD in first degree relatives and strain or impact in lumbar region are the most important risk factors identified. Other risk factors include age, body mass index, heavy physical workload, heavy weight load and persistant sitting position. Tea drinking may be a protective factor against LDDD.2. SNP id rs10908826in the vicinity of ADAMTS-4gene maybe associated with LDDD. The ratio of T homozygote in SNP id rs10908826is significantly higher in case group than in control group. rs3813623, rs3813624and rs10908826are in complete linkage disequilibrium. rs3813623is probably in the promoter region of ADAMTS-4gene. Search in TRRD database showed that a single nucleotide change in rs3813623may alter its affinity with binding of transcript factor Interferon Rgulatory Factor1(IRF1).3. Using non-conditional binary logistic regression, the T homozygosity in rs10908826appeared to be an independent risk factor besides forementioned environment factors.4. Diffusion Weighted Imaging and Diffusion Tension Imaging appeared to be reliable methods to evaluate lumbar disc degeneration. ADC values of nucleus pulposus (NP) are more related to Pfirrmann classification compared to FA values of NP. T homozygotic individuals in SNP rs10908826have lower ADC values in the L5-S1NP compared to non-homozygotes in a volunteer group. ADAMTS-4Gene maybe related to lumbar disc degeneration in Northern Han Chinese.ConclusionPossible environment risk fators in LDDD includes positive family history of LDDD in first degree relatives, strain or impact in lumbar region, age, body mass index, heavy physical workload, heavy weight load and persistant sitting position. Tea drinking may be a protective factor against LDDD. ADAMTS-4gene T homozygosity in rs3813623, rs3813624and rs10908826may be a risk factor for LDDD in Northern Han Chinese population. |
