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Báo cáo y học: "Population sequencing of two endocannabinoid metabolic genes identifies rare and common regulatory variants associated with extreme obesity and metabolite level"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Population sequencing of two endocannabinoid metabolic genes identifies rare and common regulatory variants associated with extreme obesity and metabolite level. | Harismendy et al. Genome Biology 2010 11 R118 http genomebiology.com 2010 11 11 R118 Genome Biology RESEARCH Open Access Population sequencing of two endocannabinoid metabolic genes identifies rare and common regulatory variants associated with extreme obesity and metabolite level 1.2 Ỷ 3Ỷ 4 1.2 5 1.2 Olivier Harismendy 1 11 Vikas Bansal Gaurav Bhatia 1 Masakazu Nakano 11 Michael Scott1 Xiaoyun Wang 11 C 1IniH6 Rar ll i2r 4 Ti irlr if f o6 Cir io5 c I I IÍT2 3 rìoloi I 7O6 inooi Tỉ4 7 Colette Dib 1 Edouaid lunone 1 Jack C Sipe 1 saiaii S Muiiay 1 Jean Francois Deleuze 1 Vineet Barna 1 Eric J Topol35 Kelly A r razer Abstract Background Targeted re-sequencing of candidate genes in individuals at the extremes of a quantitative phenotype distribution is a method of choice to gain information on the contribution of rare variants to disease susceptibility. The endocannabinoid system mediates signaling in the brain and peripheral tissues involved in the regulation of energy balance1 is highly active in obese patients1 and represents a strong candidate pathway to examine for genetic association with body mass index BMI . Results We sequenced two intervals covering 188 kb encoding the endocannabinoid metabolic enzymes fattyacid amide hydrolase FAAH and monoglyceride lipase MGLL in 147 normal controls and 142 extremely obese cases. After applying quality filtersz we called 11393 high quality single nucleotide variants1 55 of which are rare1 and 143 indels. Using single marker tests and collapsed marker tests we identified four intervals associated with BMI the FAAH promote the MGLL promote MGLL intron 21 and MGLL intron 3. Two of these intervals are composed of rare variants and the majority of the associated variants are located in promoter sequences or in predicted transcriptional enhances suggesting a regulatory role. The set of rare variants in the FAAH promoter associated with BMI is also associated with increased level of FAAH substrate anandamide1 further implicating