DRD2 SNP Function

[Thewonders92]

I was just curious if any of these genes are relevant to D2 functioning in the brain, as far as I've been able to gather using genes to figure out health status is impossible.

I've had addiction problems my whole life, along with depression and complete lack of motivation or joy from any activity.

I've tried SSRI's, they make the whole situation much worse.
I've tried Dexedrine without a prescription and saw a dramatic improvement, but don't want to be on non prescription medication, and don't like the idea of taking speed.

The Doctors want to get me on Seroquel again, but last time it put me completely out of commission, I couldn't motivate myself to get out of bed and eat, and lost my job. They are certain I have too much dopamine in my brain but he only saw me for 5 minutes, his assistant guessed ADHD after 20 minutes of talking to me.

I just want to be on the safe side and make sure taking a D2 antagonist is a good idea.

I'll rank mutations according to selfdecode's importance for
DRD2.
5
1) rs1076560 (A;A) 8% frequency
[URL='https://www.selfdecode.com/snp/rs1800497/']2) rs1800497 (A;A) 12% frequency[/URL]
4
3) rs12364283 (A;A) 91% frequency
[URL='https://www.selfdecode.com/snp/rs6277/']4) rs6277 (G;G) 61% frequency[/URL]
3
5) rs11214606 (C;C) 96% frequency
6) rs2242592 (A;A) 28% frequency
7) rs1079596 (T;T) 9% frequency
8) rs1079597 (T;T) 8% frequency
9) rs2734839 (C;C) 47% frequency
10) rs1799978 (T;T) 78% frequency
11) rs1800498 (G;G) 55% frequency
12) rs1801028 (G;G) 94% frequency
13) rs4648317 (G;G) 62% frequency
[URL='https://www.selfdecode.com/snp/rs6279/']14) rs6279 (C;C) 30% frequency[/URL]
[URL='https://www.selfdecode.com/snp/rs1079727/']15) rs1079727 (C;C) 7% frequency[/URL]
2
16) rs4436578 (T;T) 46% frequency
17) rs4648319 (A;A) 6% frequency
1
18) rs1800496 (G;G) 100% frequency
19) rs1125394 (C;C) 9% frequency
20) rs2283265 (A;A) 7% frequency

Links to all, and descriptions of anything relevant to D2 receptor activity or density.

1) https://www.selfdecode.com/snp/rs1076560/ (A;A)
A (minor) = Increased DRD2 signaling. Altered splicing of DRD2 protein, which decreases the ratio of D2S and D2L and subsequently increases dopamine signaling [R]. The D2 long isoform (D2L) is mainly postsynaptic and is a target for haloperidol, and the D2 short (D2S) isoform is mainly presynaptic and serves as an autoreceptor regulating (inhibiting) dopamine synthesis and release (R).

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2) https://www.selfdecode.com/snp/rs1800497/ (A;A)
G>A conversion, also known as TaqIA (or Taq1A), in the gene dopamine D2 receptor (DRD2).
G = DRD2*A2 = Wild-type allele
A = DRD2*A1 = Alternate allele
G:G (46.6%) = Normal levels of dopamine D2 receptors
G:A (41.7%) = Lower levels of dopamine D2 receptors
A:A (11.7%) = Lower levels of dopamine D2 receptors
The minor allele, A (A1), creates a dominant effect.


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3) https://www.selfdecode.com/snp/rs12364283/ (A;A)

• ]

The minor (G) allele is reported to be associated with increased levels of Striatal Dopamine D2 receptor (DRD2) [R].

• Normal levels of DRD2 (AA) [R]
• Potentially higher levels of DRD2 (GA) [R]
• Abnormally high levels of DRD2 (GG) [R].

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4) https://www.selfdecode.com/snp/rs6277/ (G;G)

• Decreased dopamine signaling (AA) [R].
• Lower DRD2 (A) [R].
• Low striatal DRD2 availability (GG) [R]
• High extrastriatal DRD2 (GG)[R]

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6) https://www.selfdecode.com/snp/rs2242592/ (A;A)

• Lower levels of DRD2 because of change in regulatory region of gene. This makes dopamine have more of an effect on the brain (G) (R).
• Normal levels of DRD2 protein in the body (A) (R).

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8) https://www.selfdecode.com/snp/rs1079597/ (T;T)

• T allele: Reduces the number of dopamine D2 receptors (in striatum) [R] [R] [R]

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13) https://www.selfdecode.com/snp/rs4648317/ (G;G)

• Possible lower levels of DRD2 protein causing higher risk for drug abuse and nicotine dependence (A) [R].
• Normal levels of DRD2 protein (GG).

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14) https://www.selfdecode.com/snp/rs6279/ (C;C)

• G (minor) allele= Decreased levels of D2 protein [R].
• C (major) allele= Normal levels of D2 protein [R].

 

[Paralee]

@Thewonders92 , I have looked at this before, I'm kind of in the same boat you are. I have just been given another atypical antidepressant to try and it indicates the CYP genes.

 

[Thewonders92]

Yeah I'm not too sure what to do regarding D2, everywhere I go, Doctors, forums, reddit all say it doesn't matter.

Though I have read TaqIa and TaqIb cause a 30 to 40% reduction in D2 receptor density, and I have them both homozygous.

I also have rs1076560 (A;A) which decreases the amount of D2 autoreceptors to D2 long receptor ratio, increasing dopamine signalling and thereby desensitizing D2 further.

And I have a gene deletion at rs1799732 (-;-) which apparently causes it's own host of issues.

There's nothing to be done about it though, everyone I've spoken to agrees they're all inconsequential.