بررسي تاثير پلي مورفيسم ها و ساير عوامل خطر بر سطح كلسترول تام خون در طول زمان با استفاده از مدل اثرات تصادفي منطقي: مطالعه قند و ليپيد تهران

Association of polymorphisms and other risk factors with cholesterol level over time using logic random effect model: Tehran Lipid and Glucose Study

ﺳﺎﺑﻘﻪ و ﻫﺪف: ﺗﻘﺎﺑﻞ ﻫﺎي ژﻧﺘﯿﮑﯽ از ﻋﻮاﻣﻞ ﻣﻮﺛﺮ ﺑﺮ ﺳﻄﺢ ﮐﻠﺴﺘﺮول ﻫﺴﺘﻨﺪ. اﯾﻦ ﺑﺮ ﻫﻢ ﮐﻨﺶ ﻫﺎ ﻣﯽ ﺗﻮاﻧﻨﺪ واﺑﺴﺘﻪ ﺑـﻪ زﻣﺎن ﺑﻮده و ﻟﺬا ﺑﺮرﺳﯽ آن ﻫﺎ در ﻃﻮل زﻣﺎن ﻧﯿﺰ ﺣﺎﺋﺰ اﻫﻤﯿﺖ ﺑﺎﺷﺪ. ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ اﯾﻦ ﮐﻪ ﺗﺎﮐﻨﻮن ﻣﻄﺎﻟﻌﻪ اي ﺑﻪ ارزﯾﺎﺑﯽ ﻃـﻮﻟﯽ اﯾﻦ ﺑﺮ ﻫﻢ ﮐﻨﺶ ﻫﺎ ﻧﭙﺮداﺧﺘﻪ اﺳﺖ، در ﻣﻄﺎﻟﻌﻪ ﺣﺎﺿﺮ، ﺗﻘﺎﺑﻞﻫﺎي ژﻧﺘﯿﮑﯽ ﻣﻮﺛﺮ ﺑﺮ ﮐﻠﺴﺘﺮول در ﻃﻮل زﻣﺎن ﺑـﺎ اﺳـﺘﻔﺎده از ﻣﺪل ﭘﯿﺸﻨﻬﺎدي اﺛﺮات ﺗﺼﺎدﻓﯽ ﻣﻨﻄﻘﯽ ﺑﺮرﺳﯽ ﺷﺪﻧﺪ. ﻣﻮاد و روش ﻫﺎ: ﻣﺪل اﺛﺮات ﺗﺼﺎدﻓﯽ ﻣﻨﻄﻘﯽ در ﻗﺎﻟﺐ ﻣﺪل ﻫﺎي اﺛﺮات ﺗﺼﺎدﻓﯽ و اﺳﺘﻔﺎده از ﻣﻘﺪار ﻣﻨﻔﯽ درﺳﺖ ﻧﻤﺎﯾﯽ ﺑﻪ ﻋﻨﻮان ﺗﺎﺑﻊ اﻣﺘﯿﺎز، ﺟﻬﺖ ﺗﺤﻠﯿﻞ ﺗﻘﺎﺑﻞ ﻫﺎ در داده ﻫﺎي ﻃﻮﻟﯽ ﺑﺎ ﭘﺎﺳﺦ ﮐﻤﯽ ﭘﯿﺸﻨﻬﺎد ﺷﺪ و ﺑﺎ اﺳـﺘﻔﺎده از آن داده ﻫـﺎي ﻃﻮﻟﯽ 329 ﻧﻔﺮ از ﺷﺮﮐﺖ ﮐﻨﻨﺪﮔﺎن ﻣﻄﺎﻟﻌﻪ ﻃﻮﻟﯽ آﯾﻨﺪه ﻧﮕﺮ ﻗﻨﺪ و ﻟﯿﭙﯿﺪ ﺗﻬﺮان ﺟﻬﺖ ﺷﻨﺎﺳﺎﯾﯽ اﺛﺮات ﻣﺘﻘﺎﺑـﻞ ﻣـﻮﺛﺮ ﺑـﺮ ﮐﻠﺴﺘﺮول در ﻃﻮل زﻣﺎن ﺗﺤﻠﯿﻞ ﮔﺮدﯾﺪ. اﺛﺮات ﻣﺘﻘﺎﺑﻞ ﺑﺎ اﺳﺘﻔﺎده از اﻟﮕﻮرﯾﺘﻢ Annealing ﺷﻨﺎﺳﺎﯾﯽ و ﺷﺪت اﺛﺮ آن ﻫـﺎ و ﻧﯿﺰ ﻣﻘﺪار ﺟﺰء ﺗﺼﺎدﻓﯽ ﻣﺪل ﺑﺎ روش ﻣﺎﮐﺰﯾﻤﻢ درﺳﺖ ﻧﻤﺎﯾﯽ ﺑﺮآورد ﺷﺪ. يافته‌ها: تركيب "مردان يا افرادي با دوركمر و فشارخون نرمال و ژنوتايپ GG براي ApoAIV" باعث كاهش معني‌دار 19/8 واحدي ((25/69 و 13/90) 95% CI) كلسترول گرديد. هم‌چنين تقابل "تري‌گليسريد بالا يا الل e2 در ApoE" باعث افزايش معني‌دار كلسترول به ميزان 16/1 واحد ((20/55 و 11/64) 95% CI) شد. كلسترول در فاز 1 مطالعه نسبت به فازهاي ديگر به‌طور معني‌‌داري (21/4 واحد (24/44 و 18/35) 95% CI) بالاتر بود. مقدار ميانگين عرض از مبدا تصادفي مدل برابر 165/82 و انحراف معيار جزء اثر تصادفي برابر 30/89 برآورد شد (0/001>p). نتيجه‌گيري: برخي از پلي‌مورفيسم‌ها و عوامل خطر داراي تاثيرات تقابلي بر كلسترول در طول زمان بودند. استفاده از روش‌ آماري پيشنهادي توانست اين بر هم‌كنش‌ها را شناسايي كند

Introduction: changes in cholesterol level can be a product of Genetic interactions of some factors. These interactions are time-dependent. Since a time-dependent genetic interaction study related to blood cholesterol levels has not been performed until now, this study is proposed to evaluate the time-dependent association of SNPs and cholesterol by using a logic random effect model of assessment. Materials and Methods: logic random effect model was proposed in the frame of random effects models by using negative likelihood as the score function to analyze the interactions related to longitudinal quantitative responses. Data of 329 participants in TLGS prospective cohort study was analyzed using proposed model to identify effective interactions related to cholesterol. Annealing algorithm was used to search interaction effects. Coefficient of these interactions and random effect were estimated using maximum likelihood method. Results: The results for male or other subjects with GG genotype for ApoAIV who had normal blood pressure and waist circumference had shown significant lower cholesterol levels (19.8 mg/dl, CI 95%: 13.9, 25.69) (p< 0.001) than other subjects without this combination. Also, having (high triglyceride or allele e2 for ApoE) was significantly associated with an increasing effect on cholesterol (β=16.1, CI 95%: 11.64, 20.55). The level of the cholesterol in phase 1 of study was 21.4 mg/dl (CI 95%: 18.35, 24.44) more than other phases (p< 0.001). The model’s random effect was estimated 165.82 with standard deviation 30.89 (p<0 .001). Conclusion: We identified some interactions among SNPs and other covariates related to cholesterol level using logic random effect model.