‏ دور تعدد اشكال جين البروتين المرتبط بالخلايا اللمفاوية التائية السامة 4 في مرضى السكري من النوع الأول في محافظة كربلاء

The Role of Cytotoxic T Lymphocyte Associated Protein-4 Gene Polymorphism in Type 1 Diabetic Patients in Kerbala Province

Abstract

Background; Type 1 diabetes mellitus (TIDM) is an insulin-dependent
form of diabetes that associated with progressively increasing morbidity and
mortality across the globe, it is usually begins in childhood and adolescence.
Development of TI1DM is a multi-steps process involving convergence of
genetic and environmental factors. Cytotoxic T lymphocyte antigen-4
(CTLA-4) encoded by the CT7LA-4 gene on chromosome 2q33 has an
important role in homeostasis and negative regulation of immune responses,
therefore CTLA-4 gene polymorphisms is considered to be a key element in
the development of T1DM. On the other hand, epidemiological data point to a
strong genetic influence on the shared susceptibility to T1DM and thyroid
diseases.
Objectives; The current study designed to the contribution of CTLA-4 (+49
A/G) (1s231775) and (-318C/T) (1s5742909) polymorphisms to the
susceptibility to T1DM, and the prevalence of thyroid diseases with T1DM in
Kerbala children.
Methods. A case-control study was designed to include 120 children with
T1DM and 120 healthy controls. The patients were diagnosed previously with
T1DM by Al-Imam Al-Hassan center for endocrine and diabetes in al-Imam
al-Hussein medical city in holy Kerbala province.
All demographic characteristics and some TIDM related variables have
been collected as data for this study.
The collection of samples were achieved during the period from Ist of
December 2017 till 30th of March 2018. Genotyping was performed using the
Tetra-primer amplification refractory mutation system polymerase chain
reaction technique (T-ARMS- PCR).
The biochemical tests were HbAlc and thyroid function test have been
performed at central laboratory of al-Imam al-Hussein medical teaching City.
while the DNA extraction and PCR done at the research laboratory of the
biomedical department of the medical college of Kerbala university.
Results; The +49A/G (18231775) polymorphism of CTLA-4 has a significant
association with TIDM. The AG genotype significantly raised the risk of
T1DM by 6 folds (OR = 6.7, 95% CI; 3.63-12.29, P<0.05). while the G allele significantly raised the risk of TIDM by two folds (OR = 2.8, 95% CI; 1.88-
4.15, P<0.05).
This polymorphism showed a significant association with T1DM
complicated with thyroid disease. The G allele significantly raised the risk of
thyroid disease in patients with T1DM by seventeen folds (OR = 17.6, 95%
CI; 2.26-137, P<0.05).
The results of the other Single Nucleotide Polymorphism -318 C/T
(rs5742909) of CTLA-4 showed non-significant differences in genotype and
allele frequencies between cases and controls, in the cases, the TT genotype in
the -318C/T polymorphism was absent and the predominant genotype in
patients as well as in the controls was CC genotype. Also, this polymorphism
was not significantly associated with T1DM complicated with thyroid disease.
Conclusion; Our case-control study suggests that the CTLA-4 (+49A/G)
gene polymorphism is associated with T1DM in Kerbala children. The G
allele of CTLA-4 (+49A/G) gene polymorphism was predisposing to thyroid
disease and T1DM.
The CTLA-4 (-318 C/T) gene polymorphism was non significantly
associated with susceptibility to T1DM.