COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Influence of OCTN2 Variants on Carnitine Status and Plasma Triglycerides

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00187733
Recruitment Status : Completed
First Posted : September 16, 2005
Last Update Posted : September 13, 2012
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
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.

Condition or disease Intervention/treatment
Carnitine Transporter Deficiency Other: Fasting blood and urine collection

Detailed Description:
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.

Layout table for study information
Study Type : Observational
Actual Enrollment : 16 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Influence of OCTN2 Variants on Carnitine Status and Plasma Triglycerides
Study Start Date : January 2005
Actual Primary Completion Date : February 2008
Actual Study Completion Date : February 2008

Group/Cohort Intervention/treatment
Other: Fasting blood and urine collection
Other: Fasting blood and urine collection
Not applicable no drugs dispensed

Biospecimen Retention:   Samples With DNA
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)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Healthy individuals per screening laboratory results and health questionnaire

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00187733

Layout table for location information
United States, California
San Francisco General Hospital
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Layout table for investigator information
Principal Investigator: Kathleen Giacomini, PhD University of California, San Francisco

Publications of Results:
Layout table for additonal information
Responsible Party: University of California, San Francisco Identifier: NCT00187733    
Other Study ID Numbers: 1005
First Posted: September 16, 2005    Key Record Dates
Last Update Posted: September 13, 2012
Last Verified: September 2012
Keywords provided by University of California, San Francisco: