Background/Purpose: Alpha7 nicotinic acetylcholine receptor (CHRNA7) is an ion channel that is gated by the binding of nicotinic ligands. Nicotine interacts with CHRNA7 leading to down-regulation of intracellular pro-inflammatory pathways. It has been suggested that smoking may protect against the development of PsA among patients with psoriasis. We aimed to study the association of CHRNA7 gene polymorphisms with PsA and their interaction with smoking.

Methods: We genotyped three groups of Caucasian individuals: patients with PsA, patients with psoriasis without arthritis (PsC) and healthy controls, for the following Single Nucleotide Polymorphisms (SNPs): rs904952, rs6494223, rs12915265, rs3826029 and rs6494165 within the CHRNA7 locus. PsA patients satisfied the CASPAR criteria. The psoriasis patients were assessed by a rheumatologist to rule out inflammatory arthritis. The control DNA was from a commercial bio-bank. Smoking status was defined as current smoker for smokers and lifetime non-smoker for non-smokers. SNP genotyping was performed using Taqman SNP Genotyping Assays run on an ABI 7900HT Real-Time PCR system. The differences in allelic and genotype distributions were compared by Chi square test and trend test using PLINK software. The frequencies of rs6494223*TT/C genotypes were then compared across the patient groups within smokers and non-smokers and the interaction term of genotype and smoking was tested using logistic regression analysis.

Results: 238 PsA patients, 219 PsC patients and 210 healthy controls were included in the study. A significant inverse association was found between the rs6494223*T/C genotype and PsA (Table 1) compared to PsC (p=0.01) and to healthy controls (p=0.01), although no significant association was found between the minor allele rs6494223*T and PsA compared to PsC (p=0.14) and to healthy controls (p=0.26). Among smokers, the minor allele rs6494223*T was inversely associated with PsA compared to PsC (Odds Ratio (OR) 0.65, p^-allele=0.04, p^-genotype=0.02) and to healthy controls (OR 0.63, p^-allele=0.02, p^-genotype=0.004). Among non-smokers, the association between rs6494223*T and PsA compared to PsC and to healthy controls was not significant (p^-allele =0.79 and 0.54, respectively). A statistically significant interaction between smoking status and rs6494223*TT genotype was found when PsA patients were compared to healthy controls (p=0.02). The remaining SNPs were not found to be associated with PsA compared to either PsC patients or to healthy controls in the entire study population and after stratification by smoking status.

Conclusion: A CHRNA7 gene polymorphism is associated with PsA. The rs649223*TT genotype may protect against the development of PsA particularly among smokers. This effect was not significant among non-smokers. This finding may explain why psoriasis patients who smoke are less likely to develop PsA.

 

Table 1 – The association between rs6494223*T/C genotype and PsA vs. PsC and healthy controls by smoking status
		PsA	PsC	P allele	P genotype	Control	P allele	P genotype
All	TT	24 (10.1%)	43 (19.7%)	0.14	0.01	39 (19.1%)	0.26	0.01
	TC	137 (57.8%)	105 (48.2%)			96 (47.1%)
	CC	76 (32.1%)	70 (32.1%)			69 (33.8%)
Smoker	TT	6 (6.5%)	27 (29.6%)	0.04	0.02	26 (23.9%)	0.02	0.004
	TC	53 (57.6%)	45 (49.5%)			49 (45%)
	CC	33 (35.9%)	19 (20.9%)			34 (31.1%)
Non-Smoker	TT	18 (12.3%)	24 (18.9%)	0.79	0.14	13 (13.4%)	0.54	0.47
	TC	85 (58.2%)	60 (47.2%)			49 (50.5%)
	CC	43 (29.5%)	43 (33.9%)			35 (36.1%)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-association-of-alpha7-nicotinic-acetylcholine-receptor-polymorphisms-with-psoriatic-arthritis-and-its-interaction-with-smoking/