Clinical trial NCT00945217: The Roles of SAH Gene Family in Athrogenic Dyslipidemia in Postmenopausal Women
Official title: Genetic Probes of Atherogenic Dyslipidemia: The Roles of the SAH Gene Family (Study 2. Postmenopausal Women)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Disorder Associated With Menstruation and/or Menopause
Dyslipidemia
Keywords: Atherogenic dyslipidemia
Non-HDL-C
Postmenopausal women
SAH gene family
Lead sponsor: Taipei Veterans General Hospital, Taiwan
Sponsor class: OTHER_GOV
First posted: 2009-07-24
Enrollment: 660
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Volunteers with natural menopause from a research clinic

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: the differences in haplotype frequencies of the SAH gene between two groups of subjects with different levels of non-HDL-C.
timeFrame: 2 years
Secondary outcomes:
measure: 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.
timeFrame: 2 years
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital
Study officials:
affiliation: Taipei Veterans General Hospital, Taiwan
name: Chii-Min Hwu, MD
role: PRINCIPAL_INVESTIGATOR
References: