Association of DNA methyltransferase polymorphisms with susceptibility to primary gouty arthritis

Abstract

and DNMT3B polymorphisms contribute to gout susceptibility. These polymorphisms were screened for in 336 gout patients and 306 healthy control subjects (from a South China population) for association with gout. The distribution frequencies of DNMT1 rs2228611 AA genotype (P=0.007) and A allele (P=0.002; odds ratio=1.508, 95% confidence �����v�l=1.158�1.964) w��� ����d �� b� ��g��fi����l� ��������d in the gout patients when compared with those in the healthy control subjects. The rs1550117 in DNMT3A and rs2424913 in DNMT3B �x��b���d �� ��g��fi���� ������������ w��� g��� susceptibility between the patients and control subjects. These results demonstrated that the DNMT1 rs2228611 polymorphism may be involved in the pathogenesis of gout, while DNMT3A rs1550117 and DNMT3B rs2424913 did not show any obvious ��g��fi����� �� ��� ������� ���d�; ����, ��� ��� b� ���d �� ���k factors to predict the susceptibility to gout. However, further studies are required to investigate the functions and regulatory mechanism of the polymorphisms of DNMTs in gout. Introduction���� ��������� �� ��� ���� ������ ����������� ��d ������ disease affecting 1-2% of adults worldwide, which is associated with elevated serum urate levels and the deposition of monosodium urate (MSU) in the joints (1). Previous studies show that gout is also associated with the genetic background, a purine rich diet and alcohol consumption (2-4), and epidemiological studies have suggested that the prevalence and incidence of gout are increasing globally (5,6). Over the past decade, signif-����� �������fi� �dv����� ��v� b��� ��d� �� ��d������d��g ��� �����g������ ��d ��������� �� g���. B���g � ����l�x d������, ��� �d����fi������ �� g������ ��d ��v���������l ���k ������� ��� gout may facilitate with investigating the pathogenesis of gout. As with other diseases, epigenetic events or heritable changes �� g��� �x�������� �������� w������ DNA ��q����� �l��������� may be evaluated to gain insight into the concrete pathogenesis of gout (7). DNA methylation is the most common epigenetic ��d�fi������, ��d �� ��������� �� ������������� ��d ��� ����-matin structure (8). The process of DNA methylation usually occurs at the CpG sites and the methyl group to the 5' position of a cytosine in a CpG dinucleotide conferred by DNA methyltransferases (DNMTs) (9). Three primary DNMTs, DNMT1, DNMT3A ��d DNMT3B, ��� �������� gl�b�l DNA ����-ylation (10). In addition, DNMT1 is a primary enzyme for maintaining methylation patterns during DNA replication, whereas DNMT3A and DNMT3B act predominantly as the de novo methyltransferases, and create novel methylation patterns (11-13).In addition, DNA methylation and its regulatory enzymes have been implicated in a diverse set of biological processes, including X chromosome inactivation, genomic imprinting, as well as autoimmunity (14)(15)(16)(17). Mutation of the human DNMTs �l���� g��� �x�������� ��d ��� ���v�d� ����g�� ���� ��� �����-nism of various diseases, such as centromere instability, acute ���l��d l��k���� ��d ������d�fi������ (18�20). T��...

Where Epigenetics Meets Food Intake: Their Interaction in the Development/Severity of Gout and Therapeutic Perspectives

“…While the identification of the genes that are targeted by non-coding RNAs remains challenging in vivo, the stability of these molecules and the possibility to easily quantify them in body fluids makes non-coding RNAs attractive circulating biomarkers (54). Additionally, the role of DNA methylation in gout was demonstrated through the discovery of a variant (rs2228611) in the DNA MethylTransferase 1 (DNMT1) gene whose presence is statistically increased in gout patients compared to controls (9). In line with this information, an innovative multi-OMICs study, in which the cell-specific methylome was compared between gout patients and controls, revealed that many differentially methylated gene regulatory genomic sites were associated with IL-1b expression in monocytes (55).…”

“…Because epigenetics has now been identified as an important player in gouty arthritis, we thought to re-evaluate the impact of diet in light of nutrient-derived epigenetic modifiers. As described in the previous section, a significant number of epigenetic factors potentially affect gout onset and can contribute to further inflammation events worsening the symptoms (9,55). Among such factors influencing epigenetic changes are multiple compounds (listed in Table 1) that are commonly found in one's diet.…”

DNMT3B-579G>T (rs1569686G>T) polymorphism and the risk of multiple sclerosis in a subset of Iranian population

“…18 Furthermore, DNMT3B-149C>T polymorphism was associated with AITDs 30 but not with primary gout arthritis in Chinese population. 31 The relationship between DNMT3B and MS was also identified recently. This study suggested that messenger ribonucleic acid (mRNA) levels of DNMTs including DNMT3B were increased and demethylation enzymes were lower in demyelinated MS hippocampus than those in myelinated MS hippocampus.…”

Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study

“…317 A study reported that the DNMT1 rs2228611 polymorphism may function in the development of gout, which is increased in patients with gout. 318 Besides, Wang et al 319 explored gout-associated enrichment of differential DNA methylation in adaptive immunity, including pathways for B and T cell receptor signalling, IL-17 signalling, and Th17 development. In another study, researchers found seven DNA methylation sites in patients with gout that map to seven genes, namely PGGT1B, UBAP1, RAPTOR, INSIG1, ANGPTL2, CNTN5, and JNK1.…”