Association of juvenile idiopathic arthritis with PTPN22 rs2476601 is specific to females in a Greek population.
BACKGROUND
Juvenile idiopathic arthritis (JIA) is an autoimmune disease characterized by persistent chronic arthritis. Disease risk is believed to be influenced by both genetic and environmental factors. It is well established that the PTPN22 single nucleotide polymorphism (SNP) rs2476601 is associated with JIA susceptibility. It was recently reported in an Australian study that this association is restricted to females and is not observed in males. A significant source of inconsistency amongst the literature on autoimmune disease susceptibility genes stems from an inability to replicate genetic findings across different racial or ethnic groups. We therefore attempted to generate further evidence of the female-specific association of rs2476601 in a homogeneous Greek population.


RESULTS
We genotyped rs2476601 in 128 Caucasian JIA patients (70.3 % female) and 221 healthy controls (28.1 % female) from Northern Greece. Overall, PTPN22 was associated with increased risk of JIA in this Greek sample (OR = 2.3, 95 % CI 1.1 - 5.1, p = 0.038). Sex-stratified analyses showed that, once again, the risk association was restricted to females (Female: OR = 19.9, 95 % CI 1.2 - 342, p = 0.0016; Male: OR = 1.1, 95 % CI 0.3 - 3.1, p = 0.94) supporting the prior findings.


CONCLUSIONS
Our data demonstrates that this sex-specific pattern of association is broadly applicable to different populations, and provides further impetus to undertake mechanistic studies to understand the impact of sex on PTPN22 in JIA.
Laboratory of Molecular Medicine and Human Genetics, Department of Medicine, Medical School of Crete, Heraklion, Greece.
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GN
Goulielmos
Genes, Environment and Complex Disease, Murdoch Childrens Research Institute, Parkville, Victoria, 3052, Australia.|Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
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RC
Chiaroni-Clarke
Rheumatology Unit, 4th Department of Internal Medicine, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece.
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Dimopoulou
Laboratory of Molecular Medicine and Human Genetics, Department of Medicine, Medical School of Crete, Heraklion, Greece.
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Zervou
Pediatric Immunology and Rheumatology Referral Center, 1st Department of Pediatrics, Aristotle University, Thessaloniki, Greece.
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Trachana
Pediatric Immunology and Rheumatology Referral Center, 1st Department of Pediatrics, Aristotle University, Thessaloniki, Greece.
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Pratsidou-Gertsi
Rheumatology Unit, 4th Department of Internal Medicine, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece.
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A
Garyfallos
Genes, Environment and Complex Disease, Murdoch Childrens Research Institute, Parkville, Victoria, 3052, Australia. justine.ellis@mcri.edu.au.|Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia. justine.ellis@mcri.edu.au.
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Ellis
D000483:Alleles; D001171:Arthritis, Juvenile / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006115:Greece / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D011110:Polymorphism, Genetic; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors
D004247:DNA; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
Gene polymorphism; Genetic association; Juvenile Idiopathic Arthritis (JIA); Protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene; Sex