Supplementary Material for: Autoimmunity-Associated <b><i>PTPN22</i></b> Polymorphisms in Latent Autoimmune Diabetes of the Adult Differ from Those of Type 1 Diabetes Patients

<b><i>Background:</i></b> A portion of adults with humoral immune changes have clinical diabetes that is initially not insulin-requiring (latent autoimmune diabetes of the adult, LADA). One of the genes strongly associated with autoimmune diabetes is <i>PTPN22</i>. We hypothesized that the manifestation and clinical features of LADA are linked to functional variants of <i>PTPN22</i>. <b><i>Methods:</i></b> We genotyped allelic frequencies of 1 protective and 3 risk-associated <i>PTPN22</i> variants in 156 Czech LADA patients, 194 type 2 diabetes mellitus patients with LADA-like progression to insulinotherapy and 324 type 1 diabetes mellitus patients, and subsequently examined the associations of <i>PTPN22</i> variants with the expression of autoantibodies and other clinical features of LADA. <b><i>Results:</i></b> We challenged the paradigm that stated that the <i>PTPN22</i> c.1858T allele serves as a risk allele for LADA, although we confirmed its risk status in the geographically matched T1DM cohort. In contrast, the frequencies of other <i>PTPN22</i> alleles (c.–1123C, c.788A and c.1970-852C) differed significantly from the healthy controls. We confirmed gender-related differences in the frequency of some <i>PTPN22</i> polymorphisms (but not c.1858C>T) in LADA. The particular <i>PTPN22</i> alleles and genotypes were associated with specific clinical features of the examined patients (autoantibodies, HbA<sub>1c</sub> and age at diagnosis of diabetes). <b><i>Conclusions:</i></b> The variability in <i>PTPN22</i> haplotypes suggests that the genetic signature of LADA is independent and should not be considered a hybrid form of T1DM and T2DM. Further studies should elucidate the associations with clinical characteristics of the LADA patients and focus on the newly emerging types of diabetes with the disease onset in early to mid-adulthood.