The R620W C/T polymorphism of the gene PTPN22 is associated with SLE independently of the association of PDCD1

The gene PTPN22 is located on chromosome 1p13 and encodes a protein tyrosine phosphatase called the lymphoid-specific phosphatase (Lyp). Lyp is expressed in lymphocytes, where it physically associates through its proline-rich motif ( called P1) with the SH3 domain of the protein tyrosine kinase Csk, an important suppressor of the Src family of kinases Lck and Fyn, which mediate TCR signaling. Therefore, it is said that interaction between Lyp and Csk enables these effectors to inhibit T-cell activation synergistically. It was reported that a missense single nucleotide polymorphism, R620W (rs2476601), 1858C --> T encodes an amino-acid change in the P1 proline-rich motif of the gene PTPN22 and is associated with SLE in North American white individuals. PTPN22 gene polymorphisms were genotyped in 571 Swedish SLE patients and 1042 healthy controls using TaqMan SNP Genotyping Assay. Differences were observed between cases and control subjects at both the allele (chi(2) = 11.2895; P = 0.0007,1df) and genotype (chi(2) = 10.2243; P = 0.0013, 1df) levels. We also found evidence of a genetic association between PTPN22 and renal disorder (chi(2) = 9.5660; P = 0.0019). We then analyzed if in patients with renal disorder associations with PDCD1 and PTPN22 were independent. Our data suggest that this appears to be the case although we observed some degree of interaction

Polymorphisms in the CTSH gene may influence the progression of diabetic retinopathy: a candidate-gene study in the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987)

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) is increasing globally, and as a consequence, more patients are affected by microvascular complications such as diabetic retinopathy (DR). The aim of this study was to elucidate possible associations between diabetes-related single-nucleotide polymorphisms (SNP) and the development of DR.METHODS: Three hundred and thirty-nine patients with T1DM from the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987) went through an ophthalmic examination in 1995; 185 of these were reexamined in 2011. The development of DR was assessed by comparison of overall DR level between baseline and follow-up in the worst eye at baseline. Patients were graded on a modified version of the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and 20 SNPs were genotyped in 130 of the 185 patients.RESULTS: We found the CTSH/rs3825932 variant (C &gt; T) was associated with reduced risk of progression to proliferative diabetic retinopathy (PDR) (OR [95 % CI] = 0.20 [0.07-0.56], p = 2.4 × 10(-3), padjust = 0.048) and ERBB3/rs2292239 variant (G &gt; T) associated with increased risk of two-step progression (OR [95 % CI] = 2.76 [1.31-5.80], p = 7.5 × 10(-3), padjust = 0.15). The associations were independent of other known risk factors, such as HbA1c, sex, and diastolic blood pressure.CONCLUSION: In conclusion, CTSH/rs3825932 and ERBB3/rs2292239 SNPs were associated with reduced risk of progression to PDR and two-step progression of DR on the ETDRS scale accordingly. The variant CTSH remained statistically significant after adjusting for multiple testing. Our results suggest an overlap between genetic variants that confer risk of T1DM and progression of DR.</p