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Contrasting association of a non-synonymous leptin receptor gene polymorphism with Wegener's granulomatosis and Churg-Strauss syndrome.
- Source :
-
Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2010 May; Vol. 49 (5), pp. 907-14. Date of Electronic Publication: 2010 Feb 25. - Publication Year :
- 2010
-
Abstract
- Objective: There is evidence that the leptin/ghrelin system is involved in T-cell regulation and plays a role in (auto)immune disorders such as SLE, RA and ANCA-associated vasculitides (AAVs). Here, we evaluate the genetic background of this system in WG.<br />Methods: We screened variations in the genes encoding leptin, ghrelin and their receptors, the leptin receptor (LEPR) and the growth hormone secretagogue receptor (GHSR). Three single nucleotide polymorphisms (SNPs) in each gene region were analysed in 460 German WG cases and 878 ethnically matched healthy controls.<br />Results: A three-SNP haplotype of GHSR was significantly associated with WG [P = 0.0067; corrected P-value (P(c)) = 0.026; odds ratio (OR) = 1.30; 95% CI 1.08, 1.57], as was one non-synonymous SNP in LEPR (Lys656Asn, P = 0.0034; P(c) = 0.013; OR = 0.72; 95% CI 0.58, 0.90). These four SNPs were re-analysed in independent cohorts of 226 German WG cases and 519 controls. While the GHSR association was not confirmed, allele frequencies of the LEPR SNP were virtually identical to those from the initial cohorts. Analysis of this SNP in the combined WG and control panels revealed a significant association of the LEPR 656Lys allele with WG (P = 0.00032; P(c) = 0.0013; OR = 0.72; 95% CI 0.60, 0.86). Remarkably, the Lys656Asn SNP showed contrasting allele distribution in two cohorts of 108 and 88 German cases diagnosed with Churg-Strauss syndrome (CSS, combined P = 0.0067; OR = 1.41; 95% CI 1.10, 1.81), whereas identical allele frequencies were revealed when comparing British WG and microscopic polyangiitis cases.<br />Conclusions: While GHSR has to be further evaluated, these data provide profound evidence for an association of the LEPR Lys656Asn SNP with AAV, resulting in opposing effects in WG and CSS.
- Subjects :
- Case-Control Studies
Female
Gene Frequency
Genetic Predisposition to Disease
Ghrelin genetics
Haplotypes genetics
Humans
Leptin genetics
Male
Middle Aged
Polymorphism, Genetic genetics
Receptors, Ghrelin genetics
White People genetics
Churg-Strauss Syndrome genetics
Granulomatosis with Polyangiitis genetics
Receptors, Leptin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1462-0332
- Volume :
- 49
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Rheumatology (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 20185531
- Full Text :
- https://doi.org/10.1093/rheumatology/kep420