Fads regulation
The present invention relates methods to increase the expression of fatty acid desaturases (FADS) and increase cellular and tissue levels of highly unsaturated fatty acids (HUFA) by modulating one or more of the FADS via the action of specific classes of drugs (e.g., statins and LXR agonists). The present invention also relates to methods of treating conditions (e.g., tumor and cancer) involving deficient function of FADS by administering statins and/or LXR agonists. The present invention further relates to methods of determining the need for statins or dietary LCPUFA in subjects.
1. A method of modulating total cholesterol, LDL, or C-reactive protein levels or treating coronary artery disease or atopic eczema in a human subject, comprising: obtaining a nucleic acid sample from the human subject; detecting whether Insertion I and Insertion II in intron 1 of the FADS2 gene are present in the nucleic acid sample; determining the need to treat the human subject with a FADS-modulating agent selected from a statin and an LXR agonist based on the detection of the absence of Insertion I and Insertion II in the nucleic acid sample; and administering a therapeutically effective amount of a statin or an LXR agonist to the human subject.
2. The method of claim 1 , wherein the statin is selected from the group consisting of simvastatin, atorvastatin, mevacor, fluvastatin, lovastatin, pravastatin, and rosuvastatin.
3. The method of claim 1 , wherein the LXR agonist is selected from the group consisting of GW3965, hypocholamide, T0901317, and N,N-dimethyl-3beta-hydroxy-cholenamide.
4. The method of claim 1 , wherein the detecting step comprises amplification with a pair of isolated oligonucleotide 5′ primer and 3′ primer to produce an amplicon.
5. The method of claim 4 , wherein the detecting step further comprises sequencing the amplicon or comparing the amplicon to a control amplicon having Insertion I or Insertion II to determine the size of the amplicon.
6. The method of claim 4 ,
wherein the 5′ primer specifically hybridizes to a sequence antisense to SEQ ID NOs: 7, 10, 11 or 23;
wherein the 3′ primer specifically hybridizes to a sequence of SEQ ID NO: 8;
wherein the 5′ primer and the 3′ primer are capable of amplifying at least partial intron 1 of the FADS2 gene indicative of presence or absence of Insertion I, and the length of the amplified sequence amplicon exceeds or equals to the combined lengths of the 5′ primer and the 3′ primer.
7. The method of claim 4 ,
wherein the 5′ primer specifically hybridizes to a sequence antisense to SEQ ID NOs: 7 or 23;
wherein the 3′ primer specifically hybridizes to a sequence of SEQ ID NOs: 8, 9, or 11;
wherein the 5′ primer and the 3′ primer are capable of amplifying at least partial intron 1 of the FADS2 gene indicative of presence or absence of Insertion I, and the length of the amplicon exceeds or equals to the combined lengths of the 5′ primer and the 3′ primer.
8. The method of claim 4 ,
wherein the 5′ primer specifically hybridizes to a sequence antisense to SEQ ID NOs: 12, or 14;
wherein the 3′ primer specifically hybridizes to a sequence of SEQ ID NOs: 13 or 23;
wherein the 5′ primer and the 3′ primer are capable of amplifying at least partial intron 1 of the FADS2 gene indicative of presence or absence of Insertion II, and the length of the amplicon exceeds or equals to the combined lengths of the 5′ primer and the 3′ primer.
9. The method of claim 4 ,
wherein the 5′ primer specifically hybridizes to a sequence antisense to SEQ ID NO: 12;
wherein the 3′ primer specifically hybridizes to a sequence of SEQ ID NOs: 13, 15 or 23;
wherein the 5′ primer and the 3′ primer are capable of amplifying at least partial intron 1 of the FADS2 gene indicative of presence or absence of Insertion II, and the length of the amplicon exceeds or equals to the combined lengths of the 5′ primer and the 3′ primer.
10. The method of claim 4 , wherein the 3′ end nucleotide of the 5′ primer hybridizes to a nucleotide which is within the antisense sequence of Insertion I or Insertion II.
11. The method of claim 4 , wherein the 3′ end nucleotide of the 3′ primer hybridizes to a nucleotide which is within the sequence of Insertion I or Insertion II.
12. The method of claim 10 , wherein the 3′ end nucleotide of the 5′ primer does not form Watson-Crick base pair with the nucleotide if the intron 1 of the FADS2 gene to be amplified lacks Insertion I or Insertion II.
13. The method of claim 11 , wherein the 3′ end nucleotide of the 3′ primer does not form Watson-Crick base pair with the nucleotide if the intron 1 of the FADS2 gene to be amplified lacks Insertion I or Insertion II.