Expired Study
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San Francisco, California 94143


The current study is part of a large multi-investigator grant to look at the pharmacogenetics of a number of membrane transporters. Previously, the investigators have recruited a cohort of healthy volunteers (Studies of Pharmacogenetics in Ethnically-Diverse Populations, or SOPHIE) and have resequenced the coding region of a number of membrane transporter genes to identify genetic polymorphisms in these genes. Subjects in this cohort have agreed to be called back for recruitment in further studies based on their own genetic sequence, allowing the investigators the possibility to prospectively study the influence of genetic polymorphisms on particular phenotypes (i.e., genotype-to-phenotype studies). The investigators plan to take a genotype-to-phenotype approach to study the influence of specific polymorphisms in the novel organic cation transporter 2 (OCTN2) gene on carnitine and lipid metabolism in healthy subjects.

Study summary:

Although OCTN2 is fairly well studied in its relationship with SCD, little is known about the carrier frequency of disease-causing alleles of OCTN2, or of more common functional polymorphisms in this gene. To address these issues, we screened for genetic variants in the OCTN2 coding region by direct sequencing of the exons and flanking intronic region of OCTN2 in a large sample (n = 276) of ethnically diverse subjects. In addition, we established lymphoblastoid cell lines from subjects homozygous for either allele of the previously identified promoter region variant, -207G>C. We found eight amino acid sequence variants of OCTN2, of which three (Phe17Leu, Leu144Phe, and Pro549Ser) were polymorphic in at least one ethnic group. When assayed for functional activity by expression in human embryonic kidney 293 cells, using as probes both the endogenous substrate (l-carnitine) and the organic cation tetraethylammonium, three variants showed functional differences from the reference OCTN2 (Phe17Leu, Tyr449Asp, Val481Phe; p < 0.05). Further studies of the Phe17Leu polymorphism showed a reduced V(max) for l-carnitine transport to approximately 50% of the reference OCTN2. Confocal microscopy studies using an OCTN2-GFP fusion protein showed that Phe17Leu had distinct subcellular localization from the reference OCTN2, with diffuse cytoplasmic retention of Phe17Leu, in contrast to reference OCTN2, which localized specifically to the plasma membrane. Lymphoblasts from subjects homozygous for the -207G allele showed increased l-carnitine transport compared with the -207C/C homozygotes (p < 0.05). This study suggests that although loss-of-function mutations in OCTN2 are likely to be rare, common variants of OCTN2 found in healthy populations may contribute to variation in the disposition of carnitine and some clinically used drugs.


Inclusion Criteria: - Previous participation in the "SOPHIE" study - Between the ages of 18 and 40 years old - Have a pre-selected genotype for OCTN1 and OCTN2 - Have been selected as healthy by medical history questionnaire and screening blood work (complete blood count [CBC], comprehensive metabolic panel). Exclusion Criteria: - Pregnant at the time of the study - Have a new history indicating they are no longer healthy - Taking a medication that could confound study results - Individuals with anemia (hemoglobin < 12 g/dL), an elevation in liver enzymes to higher than double the respective normal value, or elevated creatinine concentrations (males ≥ 1.5 mg/dL, females ≥ 1.4 mg/dL). - Do not consent to participate in the study.

Study is Available At:

Original ID:




Secondary ID:

Study Acronym:

Brief Title:

Influence of OCTN2 Variants on Carnitine Status and Plasma Triglycerides

Official Title:

Influence of OCTN2 Variants on Carnitine Status and Plasma Triglycerides

Overall Status:


Study Phase:




Minimum Age:

18 Years

Maximum Age:

40 Years

Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of California, San Francisco

Oversight Authority:

United States: Institutional Review Board

Reasons Why Stopped:

Study Type:


Study Design:

Observational Model: Cohort, Time Perspective: P

Number of Arms:


Number of Groups:


Total Enrollment:


Enrollment Type:


Overall Contact Information

Official Name:Kathleen Giacomini, PhD
Principal Investigator
University of California, San Francisco

Study Dates

Start Date:January 2005
Completion Date:February 2008
Completion Type:Actual
Primary Completion Date:February 2008
Primary Completion Type:Actual
Verification Date:September 2012
Last Changed Date:September 11, 2012
First Received Date:September 14, 2005

Study Outcomes

There are no available Study Outcomes

Study Interventions

Intervention Type:Other
Name:Fasting blood and urine collection
Description:Not applicable no drugs dispensed
Arm Name:Fasting

Study Arms

Study Arm Type:Other
Arm Name:Fasting
Description:Other: Fasting blood and urine collection

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:University of California, San Francisco

Samples and Retentions

Sample Retention:Samples With DNA
Description: Blood Draw (10cc) to determine eligibility (CBC, blood chemistries). Blood draw (20cc) at t=0 in fasting state for baseline measurement of biochemical markers (including carnitine, acylcarnitines, creatinine, and total lipid panel) Urine collection at t=0 Blood draw (20cc) at t=2 hours for measurement of biochemical markers (including carnitine, acylcarnitines, creatinine, and total lipid panel) Urine collection at t=2 hours Transformation of blood to establish lymphoblastoid cell lines (from blood samples collected at t=0 and t=2 hours)
Study Population: Healthy individuals per screening laboratory results and health questionnaire
Sample Method:Non-Probability Sample

Study References

Reference Type:Results Reference
Citation:Urban TJ, Gallagher RC, Brown C, Castro RA, Lagpacan LL, Brett CM, Taylor TR, Carlson EJ, Ferrin TE, Burchard EG, Packman S, Giacomini KM. Functional genetic diversity in the high-affinity carnitine transporter OCTN2 (SLC22A5). Mol Pharmacol. 2006 Nov;70(5):1602-11. Epub 2006 Aug 24.

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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