HTR2A

Gene Name:

5-hydroxytryptamine (serotonin) receptor 2A

Chromosome:

13

Chromosomal Location:

47,407,513: 47,470,369

Entrez Gene ID:

3356

OMIM ID:

182135

Protein Name:

5-hydroxytryptamine receptor 2A; serotonin receptor, 2A

UNIPROT ID:

P28223

Function:

receptor for the neurotransmitter serotonin

Phenotype/Disease:

musculoskeletal pain, irritable bowel syndrome, analgesia requirements, other

Pain Data in Humans:

HTR2A-v1

Variant Type:

common polymorphism

Variant ID:

T102C

Phenotype/Disease:

Analgesia requirements after abdominal surgery, fibromyalgia symptoms, temporomandibular dysfunction

SNP ID:

rs6313

SNP Type:

synonymous

Minor Allele:

T

Phenotype of Minor Allele:

Increased total frequency of use of rescue analgesics and antipyretics (after surgery), higher pain score or lower pain threshold (in fibromyalgia)

Notes:

Aoki et al., 2002 found significant interaction between the SNP and sex for analgesic requirement. Mutlu et al., 2004 report that the CC genotype is overrepresented in patients with temporomandibular dysfunction.

Negative studies: This polymorphism was not associated with fibromyalgia case status in Gursoy et al., 2001, Bondy et al., 1999, Tander et al., 2008 or Matsuda et al., 2010. Klepstad et al., 2011 found no significant associations of any 5HTR2A SNPs with opioid dose for cancer pain in cancer pain patients.

HTR2A-v2

Variant Type:

common polymorphism

Variant ID:

-1438G>A

Phenotype/Disease:

Pain in chronic fatique syndrome

SNP ID:

rs6311

SNP Type:

5' noncoding

Minor Allele:

T

Phenotype of Minor Allele:

Increased risk of arthralgia in females with chronic fatigue syndrome

Reference(s):

Ortega-Hernandez et al., 2009

Notes:

Negative studies: Tander et al., 2008 (fibromyalgia).

HTR2A-v3

Variant Type:

common polymorphisms

Phenotype/Disease:

Irritable bowel syndrome

SNP ID:

rs6313, rs6311

SNP Type:

synonymous, 5' noncoding

Minor Allele:

T, T

Phenotype of Minor Allele:

Increased risk of irritable bowel syndrome for homozygote C (major) allele of rs6313 and homozygote A (minor) allele of rs6311. rs6316 minor allele T/T genotypes had higher reported chronic abdominal pain.

Reference(s):

Pata et al., 2004

HTR2A-v4

Variant Type:

common polymorphisms

Phenotype/Disease:

Somatic symptoms in general population

SNP ID:

rs9567746, rs2274639

SNP Type:

intronic, upstream, intronic

Minor Allele:

G, G

Phenotype of Minor Allele:

Increased somatic symptoms for rs9567746; decreased somatic symptoms for rs2274639

Reference(s):

Holliday et al., 2010

Notes:

Reseachers looked at 143 SNPs in serotonin pathway candidate genes in 967 subjects. HTR2A associations remained significant after adjusting for anxiety, depression and maximum number of pain sites.

HTR2A-v5

Variant Type:

common polymorphisms

Phenotype/Disease:

Chronic widespread pain

SNP ID:

rs12584920, rs17289394, rs9534511

SNP Type:

intronic, upstream, intronic

Minor Allele:

T, A, T

Phenotype of Minor Allele:

Increased risk of chronic widespread pain (rs12584920), increased total number of pain sites (rs17289394), decreased total number of pain sites (rs9534511)

Reference(s):

Nicholl et al., 2011

Notes:

SNP associations found in discovery cohort confirmed in a replication cohort and metanalysis. Total sample size 3474.

HTR2A-v6

Variant Type:

common polymorphisms

Phenotype/Disease:

temporomandibular disorders

SNP ID:

rs9316233

SNP Type:

intronic, upstream, intronic

Minor Allele:

G

Phenotype of Minor Allele:

lower risk of TMD

Reference(s):

Smith et al., 2011

Notes:

In Smith et al., 2011, no SNPs achieved a strict experiment-wide significance threshold, but the results support a role for the gene in TMD as suggeseted by Mutlu et al., 2004.

HTR2A-v7

Variant Type:

common polymorphism

Phenotype/Disease:

Somatization (including pain) in major depression

SNP ID:

rs9534505

SNP Type:

intronic

Minor Allele:

A

Phenotype of Minor Allele:

Decreased somatization score for AA/AG genotypes compared to GG phenotype

Reference(s):

Klengel et al., 2011

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