**2.13 OSBPL11 (ORP11)**

136 Dyslipidemia - From Prevention to Treatment

As a result, we found that the LDL cholesterol of individuals with the rs2290532 (D254N) polymorphism was significantly greater in subjects with the CC+CT genotype than in subjects with the TT genotype (124.3+/-1.3 vs. 111.6+/-4.1 mg per 100 ml, P=0.009) (Fig. 3). Comparison of the genotype frequency in both groups indicated that the genotype associated with low risk (TT) reduced the risk of hyper-LDL cholesterolemia significantly (P=0.003), with an odds ratio of 0.35 (95% confidence interval=0.17-0.76). These findings suggest that the rs2290532 (D254N) polymorphism in OSBPL10 may predispose individuals

Perttila et al. also reported that the analysis of variants in ORP10 gene revealed suggestive linkage of ORP10 single-nucleotide polymorphisms (SNPs) with extreme end high TG (>90th percentile) trait. They carried out an association analysis in a metabolic syndrome subcohort (Genmets) of Health2000 examination survey (N = 2,138), revealing an association

The result proves that ORP10 is genetically associated with both TG and LDL cholesterol levels. Though it is estimated that microtubule dependent intracellular transport of vesicles

Fig. 2. Intracellular localization of ORP10.

with this SNP to hyper-LDL cholesterolemia.

Fig. 3. Relation of rs2290532 of ORP10 with serum LDL cholesterol.

of multiple ORP10 SNPs with high serum TG levels (>95th percentile).

**Structure, Tissue distribution and Intracellular localization:** ORP11 belongs to the subfamily VI of OSBP/ORP homologues. ORP11 has an ORD and a PH domain but does not have an FFAT motif or a transmembrane domain. ORP11 is present at the highest levels in human ovary, testis, kidney, liver, stomach, brain, and adipose tissue. Immunohistochemistry demonstrates abundant ORP11 in the epithelial cells of kidney tubules, testicular tubules, caecum, and skin. ORP11 dimerizes with ORP9 and localizes at the Golgi-late endosome interface (Zhou, Li et al. 2010).

**Molecular functions related to dyslipidemia:** Cells overexpressing ORP11 displayed lamellar lipid bodies associated with vacuolar structures or the Golgi complex, indicating a disturbance of lipid trafficking. Similar multilamellar membranes arise in endo-lysosomal compartments in phospholipidosis occurring, for instance, upon incubation of macrophage with oxidized low-density lipoprotein, or associated with inheritable lysosomal storage disorders, situations in which normal lipid transport is disturbed. These findings indicate that ORP11, in interaction with ORP9, may act as an intracellular lipid sensor or transporter.

**Epidemiological study:** it is reported that ORP11 is significantly overexpressed in the visceral adipose tissue of obese men with metabolic syndrome (Bouchard, Faucher et al. 2009). Furthermore, they found SNPs in the ORP11 gene to be associated with several cardiovascular risk factors in obese individuals. IVS12+95 T>C, a newly discovered SNP of the study, was associated with LDL cholesterol levels (OR = 1.63; P < 0.001), hyperglycemia/diabetes (OR = 1.48; P < 0.004) as well as with metabolic syndrome per se (OR = 1.56; P < 0.01). These results suggest that ORP11 is involved in cholesterol and glucose metabolism in obese individuals.
