The 14 bp Del/Ins HLA-G Polymorphism Is Related with High Blood Pressure in Acute Coronary Syndrome and Type 2 Diabetes Mellitus

Abstract

Immunologic and inflammatory processes are involved in the pathogenesis of acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM2). Human leukocyte antigen-G (HLA-G) is a negative regulator of the immune response. This study evaluates the 14 bp Del/Ins HLA-G polymorphism in ACS and DM2. Three hundred and seventy individuals from Western Mexico were recruited and categorized into three groups: ACS (86), DM2 without coronary complications (70), and healthy subjects (214). Genotyping of the 14 bp Del/Ins HLA-G polymorphism was performed by PCR and Native-PAGE. The most common risk factors were hypertension and overweight in ACS and DM2, respectively. The genetic distribution of the 14 bp Del/Ins HLA-G polymorphism showed no significant differences between groups (P ≥ 0.23). Nonetheless, the Ins/Ins genotype was associated with high blood pressure (HBP) in the DM2 group (ORc = 1.65, P = 0.02). The genetic recessive model showed similar findings (ORc = 3.03, P = 0.04). No association was found in ACS, with a P of 0.05; nevertheless, the prevalence of Ins/Ins carriers was quite similar to that found in the DM2-HBP group. The 14 bp Del/Ins HLA-G polymorphism was not a susceptibility factor for ACS or DM2; however, the Ins/Ins genotype might have contributed to the development of HBP in the studied groups.

Influence of hormones on the immunotolerogenic molecule HLA-G: a cross-sectional study in patients with congenital adrenal hyperplasia

“…Moreover, diseases in which RAS is activated (i.e. heart failure with reduced ejection fraction and hypertension) present with increased soluble HLA-G (27,28).…”

HLA-G Molecules in Autoimmune Diseases and Infections

“…These data suggest a possible implication of HLA-G antigens in the diabetic condition. In fact, SNPs rs4122198, rs2394186, rs1619379 , and rs1611133 near the HLA-G gene have been associated with type 1 diabetes ( 93 ); dendritic cells from type 1 diabetic patients produce lower HLA-G molecules in response to IFN-beta ( 94 ) in comparison with control subjects and the HLA-G 14bp INS-INS genotype might contribute to the development of high blood pressure in type 2 diabetes ( 95 ).…”

HLA‐G 14‐bp Ins/Ins Genotype in Patients Harbouring Helicobacter pylori Infection: A Potential Risk Factor?

“…In particular, the 14‐bp Ins / Del polymorphism in the +2960 position at the 3′UTR region of HLA‐G gene is associated with HLA‐G mRNA isoform alternative splicing patterns and stability and thus may influence HLA‐G protein level and function . The Ins allele has been associated with an alternative splicing in which 92 b are removed from a primary mRNA transcript, which leads to diminished levels of HLA‐G mRNA and reduced circulating soluble HLA‐G isoforms . On the other hand, the Del allele is associated with increased mRNA stability.…”

“…HLA‐G polymorphisms and HLA‐G soluble levels have been associated with the outcome of different disorders such as recurrent abortion , systemic lupus erythematosus , juvenile idiopathic arthritis and rheumatoid arthritis , multiple sclerosis , cancer and acute coronary syndrome , among others. However, there is still no consensus about the exact role of this molecule in the studied disorders.…”