The Roles of SAH Gene Family in Athrogenic Dyslipidemia in Postmenopausal Women

Dyslipidemia Clinical Trial

— MOSAH-S2  

Official title:

Genetic Probes of Atherogenic Dyslipidemia: The Roles of the SAH Gene Family (Study 2. Postmenopausal Women)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00945217
• Other study ID #: 98-01-63A
• Status: Recruiting
• Phase: N/A
• First received: April 17, 2009
• Last updated: December 5, 2011
• Start date: October 2009
• Est. completion date: July 2012

Study information

• Verified date: December 2011
• Source: Taipei Veterans General Hospital, Taiwan
• Contact: Chii-Min Hwu, MD
• Phone: 886228757516
• Email: chhwu[@]vghtpe.gov.tw
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Observational

Clinical Trial Summary

Atherogenic dyslipidemia is characterized by high levels of apolipoprotein B (apoB)-containing lipoproteins, including very-low-density lipoprotein (VLDL) and its remnants and small, dense LDL (sdLDL) particles, and reduced levels of high-density lipoprotein cholesterol (HDL-C). The National Cholesterol Education Program (NCEP) recommended using non-high-density lipoprotein cholesterol (non-HDL-C) to surrogate atherogenic lipoproteins in clinical practice. Recently, the investigators have done a pilot study to study the associations between SAH gene variants and atherogenic dyslipidemia (surrogated by non-HDL-C) in postmenopausal women. The investigators found that homozygosity for SAH haplotype 3 was associated with increased adiposity, insulin resistance, and elevated levels of non-HDL-C in the postmenopausal women. Based on the findings of the pilot study, the investigators plan to expand the cohort of postmenopausal women to about 800 women, that is, recruited 660 new subjects in two years. The associations between non-HDL-C and the SAH gene family will be done. Fasting blood sampling for buffy coats and lipids is the core test of Study 2. A 75-g oral glucose tolerance test (OGTT) will be available as an optional test for a better phenotyping of insulin resistance for the participants. Detailed lipid profiling including measurements of VLDL cholesterol, VLDL-TG, remnant lipoprotein, LDL particle size, apoA1, apoB, and apoCIII will be done in the second year of the study if significant associations between gene variants of the SAH gene family and non-HDL-C are detected.

Description:

Atherogenic dyslipidemia is characterized by high levels of apolipoprotein B (apoB)-containing lipoproteins, including very-low-density lipoprotein (VLDL) and its remnants and small, dense LDL (sdLDL) particles, and reduced levels of high-density lipoprotein cholesterol (HDL-C). Extensive evidence shows that atherogenic dyslipidemia contributes not only to residual macrovascular risk but also to inflammation and microvascular complications. The National Cholesterol Education Program (NCEP) recommended using non-high-density lipoprotein cholesterol (non-HDL-C) to surrogate atherogenic lipoproteins in clinical practice. Elevated non-HDL-C may represent abnormal secretion, abnormal catabolism, and/or abnormal hepatic uptake of triglycerides (TG)-rich lipoproteins. Recently, we have done a pilot study to study the associations between SAH gene variants and atherogenic dyslipidemia (surrogated by non-HDL-C) in postmenopausal women. We found that homozygosity for SAH haplotype 3 was associated with increased adiposity, insulin resistance, and elevated levels of non-HDL-C in the postmenopausal women. Moreover, researchers have identified that there are at least four members in the SAH gene family: SAH, MACS1, MACS2, and MACS3. All of them seem to have acyl-CoA synthetase activity toward medium-chain fatty acids and all are clustered in chromosome 16p12. In the present study, we propose to do a two-year study to examine the associations between the SAH gene family and atherogenic dyslipidemia in postmenopausal women.

Based on the findings of the pilot study, we plan to expand the cohort of postmenopausal women to about 800 women, that is, recruited 660 new subjects in two years. The associations between non-HDL-C and the SAH gene family will be done 18 months after the study started. Fasting blood sampling for buffy coats and lipids is the core test of Study 2. A 75-g oral glucose tolerance test (OGTT) will be available as an optional test for a better phenotyping of insulin resistance for the participants. Detailed lipid profiling including measurements of VLDL cholesterol, VLDL-TG, remnant lipoprotein, LDL particle size, apoA1, apoB, and apoCIII will be done in the second year of the study if significant associations between gene variants of the SAH gene family and non-HDL-C are detected.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 660
• Est. completion date: July 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Naturally postmenopausal women

• Not menstruated within the last 12 months.

• Willing to participate by signing an informed consent

Exclusion Criteria:

• Patients of known history of type 2 diabetes.

• Those with fasting glucose = 126 mg/dL.

• History of major renal, liver, heart, and neurological disease.

• History of hyperthyroidism or hypothyroidism.

• History of acute illness in the past 6 months.

• History of alcoholism or drug abuse.

• Women who are pregnant.

• Current or concomitant illness that would interfere with the subject's ability to perform the study or that would confound the study results, judged by the investigation physicians.

• Any concomitant medication within 2 weeks of the study.

• Difficult venous access

Study Design

Observational Model: Cohort, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Disorder Associated With Menstruation and/or Menopause
• Dyslipidemia
• Dyslipidemias

Locations

Country	Name	City	State
Taiwan	Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Taipei Veterans General Hospital, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the differences in haplotype frequencies of the SAH gene between two groups of subjects with different levels of non-HDL-C.		2 years	No
Secondary	the differences in haplotype frequencies of other members of the SAH gene family between two groups of subjects with different levels of non-HDL-C.		2 years	No