Cyclic AMP-Responsive Element Modulator α Polymorphisms Are Potential Genetic Risks for Systemic Lupus Erythematosus.
Qian Guo1, Xuyong Chen1, Yan Du1
1Department of Rheumatology & Immunology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China.
Journal of Immunology Research
|November 25, 2015
Summary
Genetic variations in cyclic AMP-responsive element modulator alpha (CREMα) single nucleotide polymorphisms (SNPs) rs2295415 and rs1057108 are associated with systemic lupus erythematosus (SLE) susceptibility. These CREMα SNPs may influence specific clinical manifestations in SLE patients.
Area of Science:
- Genetics
- Immunology
- Rheumatology
Background:
- Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a significant genetic component.
- The role of cyclic AMP-responsive element modulator alpha (CREMα) in SLE pathogenesis remains largely unexplored.
- Identifying novel genetic factors is crucial for understanding SLE susceptibility and developing targeted therapies.
Purpose of the Study:
- To investigate the association between CREMα single nucleotide polymorphisms (SNPs) and SLE susceptibility.
- To explore potential correlations between specific CREMα SNPs and clinical/serologic features of SLE.
Main Methods:
- Genotyping of four tag SNPs (rs1057108, rs2295415, rs11592925, rs1148247) in 889 SLE cases and 825 healthy controls.
- Association analyses using age- and sex-adjusted logistic regression.
- Haplotype analysis and stratification by clinical/serologic subsets.
Main Results:
- Increased frequencies of the G allele for rs2295415 (OR 1.244, P=0.019) and rs1057108 (OR 1.165, P=0.049) in SLE patients compared to controls.
- A significant association of the 'G-G' haplotype (rs1057108 and rs2295415) with SLE susceptibility (OR 1.454, P=0.00056).
- rs2295415 showed a suggestive association with anti-Sm antibodies-positive SLE (OR 1.382, P=0.044) and a potential protective effect in SLE patients with renal disorder (OR 0.745, P=0.032).
Conclusions:
- CREMα SNPs rs2295415 and rs1057108 represent novel genetic susceptibility factors for SLE.
- SNP rs2295415 may increase the risk for anti-Sm antibodies-positive SLE and offer protection against lupus nephritis.
- Further research is warranted to elucidate the functional mechanisms of CREMα in SLE pathogenesis.
Related Concept Videos
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
109
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
109
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
68
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
68
01:27Principles of Pharmacogenetics: Types of Genetic Variants
95
The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
95
01:19Hypersensitivity Reactions: Immune-Complex Reactions
149
Type III hypersensitivity reactions occur when antigen–antibody complexes form and activate the complement system. Normally, these complexes help the clearance of antigens by phagocytes and red blood cells. However, when large numbers of immune complexes are present, they can deposit in tissues—particularly in the walls of blood vessels—leading to inflammation and tissue injury. These deposits trigger complement activation and neutrophil recruitment, resulting in serum...
149
01:29Autoimmune Disorders
2.2K
Autoimmune diseases are a group of disorders in which the body's immune system mistakenly attacks its own cells, tissues, and organs. This results from an overactive immune response against substances and tissues normally present in the body. Let's delve into the concept and mechanism of autoimmune diseases from an immune system point of view, explore different causes and examples of such diseases, and discuss potential solutions.
Concept and Mechanism of Autoimmune Diseases
The immune...
Concept and Mechanism of Autoimmune Diseases
The immune...
2.2K
01:29Pharmacogenomics: Identification of New Drug Targets
76
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
76