PTPN22 intron polymorphism rs1310182 (c.2054-852T>C) is associated with type 1 diabetes mellitus in patients of Armenian descent

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F23%3A43925779" target="_blank" >RIV/00216208:11120/23:43925779 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1371/journal.pone.0286743" target="_blank" >https://doi.org/10.1371/journal.pone.0286743</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0286743" target="_blank" >10.1371/journal.pone.0286743</a>

Result language

angličtina

Original language name

PTPN22 intron polymorphism rs1310182 (c.2054-852T>C) is associated with type 1 diabetes mellitus in patients of Armenian descent

Original language description

Protein tyrosine phosphatase, nonreceptor type 22 (PTPN22), is an archetypal non-HLA autoimmunity gene. It is one of the most prominent genetic contributors to type 1 diabetes mellitus outside the HLA region, and prevalence of its risk variants is subject to enormous geographic variability. Here, we address the genetic background of patients with type 1 diabetes mellitus of Armenian descent. Armenia has a population that has been genetically isolated for 3000 years. We hypothesized that two PTPN22 polymorphisms, rs2476601 and rs1310182, are associated with type 1 diabetes mellitus in persons of Armenian descent. In this association study, we genotyped the allelic frequencies of two risk-associated PTPN22 variants in 96 patients with type 1 diabetes mellitus and 100 controls of Armenian descent. We subsequently examined the associations of PTPN22 variants with the manifestation of type 1 diabetes mellitus and its clinical characteristics. We found that the rs2476601 minor allele (c.1858T) frequency in the control population was very low (q = 0.015), and the trend toward increased frequency of c.1858CT heterozygotes among patients with type 1 diabetes mellitus was not significant (OR 3.34, 95% CI 0.88-12.75; χ2 test p &gt; 0.05). The control population had a high frequency of the minor allele of rs1310182 (q = 0.375). The frequency of c.2054-852TC heterozygotes was significantly higher among the patients with type 1 diabetes mellitus (OR 2.39, 95% CI 1.35-4.24; χ2 test p &lt; 0.001), as was the frequency of the T allele (OR 4.82, 95% CI 2.38-9.76; χ2 test p &lt; 0.001). The rs2476601 c.1858CT genotype and the T allele correlated negatively with the insulin dose needed three to six months after diagnosis. The rs1310182 c.2054-852CC genotype was positively associated with higher HbA1c at diagnosis and 12 months after diagnosis. We have provided the first information on diabetes-associated polymorphisms in PTPN22 in a genetically isolated Armenian population. We found only a limited contribution of the prototypic gain-of-function PTPN22 polymorphism rs2476601. In contrast, we found an unexpectedly close association of type 1 diabetes mellitus with rs1310182.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30101 - Human genetics

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

PLoS One

ISSN

1932-6203

e-ISSN

1932-6203

Volume of the periodical

18

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

"e0286743"

UT code for WoS article

001010646600019

EID of the result in the Scopus database

2-s2.0-85161973528