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Association analyses of the INSIG2 polymorphism in the obesity and cholesterol levels of Korean populations

DOI: 10.1186/1471-2350-10-96

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The rs7566605 polymorphism was genotyped with 2,364 Koreans, and associations with obesity- and cholesterol-related traits were analyzed statistically via an ANOVA or T-test.Replication of an association with BMI, WHR, fat mass, fat percent, and abdominal fat area failed, and the C allele of rs7566605 was not associated significantly with total cholesterol, HDL cholesterol, or triglyceride. However, it was found in a meta-analysis of a dominant model that the C allele of rs7566605 appeared to affect the level of the total cholesterol, especially in female subjects.We failed to show associations of rs7566605 with cholesterol- and obesity-related phenotypes, although we newly suggest the possible involvement of INSIG2 with the plasma level of the total cholesterol in women.INSIG2 is considered to be a candidate gene with respect to involvement in the development of obesity. A common variant located 10 kb upstream of the gene, rs7566605, was found to be associated with BMI in a recent genome-wide association study [1]. This association has been suitably replicated in several white [1-3], African-American [1], and Asian populations [4-6]. However, the SNP did not have a genetic effect on obesity according to other studies including white [2,7-14], Afro-Caribbean [12], and Asian populations [15-17]. Hence, the INSIG2 polymorphism may have an important effect in overweight populations under certain environmental circumstances, given several positive associations found in studies of overweight subjects [3,4].INSIG2 has attracted the attention of researchers due to its role in cholesterol metabolism [18]. The protein is known to reside in the endoplasmic reticulum, where it binds to SCAP to inhibit it from convoying SREBPs to the Golgi apparatus [18]. Eventually, INSIG2 prevents SREBP from activating cholesterol synthesis because SREBP cannot be processed and activated by the Golgi enzymes. These actions of INSIG2 were also reported in subsequent research involving mice [18

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