Polymorphisms of Renin-Angiotensin-Aldosterone System Gene in Chinese Han Patients with Nonfamilial Atrial Fibrillation

Abstract

BackgroundAtrial fibrillation(AF) is the most common arrhythmia in the adult population. The activated renin-angiotensin-aldosterone system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation. The aim of this study was to investigate the association between nonfamilial AF and polymorphisms in RAS gene.MethodsA total of 931 patients with nonfamilial AF, 663 non-AF heart disease patients and 727 healthy subjects were selected. 10 tagSNPs (tSNPs) (ACE gene rs8066114, AGT gene rs7539020, rs3789678, rs2478544, rs11568023, rs2478523, rs4762, rs699 and CYP11B2 rs3802230, rs3097) were chosen and genotyped in our study. Single-locus analysis and haplotype analysis were used in this study.ResultsIn single-locus analysis, we found rs11568023 and rs3789678 in AGT gene were associated with nonfamilial AF in Chinese Han population. AF risk was associated with rs3789678 between the AF group and control groups. Under dominant model, the significant AF risk was observed in rs3789678 between the AF group and non AF heart control group; And the protective effect was found in rs11568023, compared with the non-AF heart disease control group. In multilocus haplotype analysis, the association between frequencies of the haplotypes and AF risk was showed in AGT gene (rs7539020-rs3789678), compared ‘TT’ haplotype with the common ‘TC’ haplotype, adjusted for age, gender, LVEF, LVEDD, LAD and frequency of hypertension and diabetes. The diplotype with ‘TC’, carrying rs3789678-C-allele, was associated with reduced risk of AF between the AF group and the healthy control group. The diplotype with ‘TT’ haplotype in the same block, carrying rs3789678-T-allele, was associated with increased risk of AF.ConclusionsVia a large-scale case-control study, we found that rs3789678 site was potential susceptible locus of AF whereas rs11568023 was protective factor.

Relationship Between ABCB1 Polymorphisms and Cold Pain Sensitivity Among Healthy Opioid‐naive Malay Males

“…We speculate that the CGC/CGC diplotype may cause the target cells within the CNS to have impaired transport of its substrates, including endogenous opioid peptide β‐endorphin, from its site of action in the brain into the blood. β‐Endorphin is well known to be involved in the modulation of pain transmission, and it produces analgesia by inhibiting the firing of peripheral somatosensory fibers . As a result of increased β‐endorphin levels in the brain, a better response to experimental cold pain stimuli is therefore observed.…”

“…b-Endorphin is well known to be involved in the modulation of pain transmission, and it produces analgesia by inhibiting the firing of peripheral somatosensory fibers. 63 As a result of increased bendorphin levels in the brain, a better response to experimental cold pain stimuli is therefore observed. Thus, CGC/CGC diplotype for the c.1236C>T, c.2677G>T/A, and c.3435C>T polymorphisms may predict a lower sensitivity to cold pain stimuli as evidenced by a significantly higher cold pain threshold and cold pain tolerance than those without the diplotype.…”

The Genetic Puzzle of Familial Atrial Fibrillation

“…GATA and PITX2 genes affect the development of the pulmonary venous myocardium which is involved in the initiation of AF ( Table 1). Several studies reported an increased risk of AF with polymorphism of RAAS system genes encoding angiotensin converting enzyme inhibitor, angiotensin gene promotor, and angiotensinogen (24,65).…”

Molecular genetic markers of atrial fibrillation

“…Ренин-ангиотензиновая система играет важную роль в патогенезе ФП [41], в частности, имеются исследования о роли генов ACE, AGT и AGTR1 в формировании предрасположенности к развитию данной патологии. Молекулярно-генетические маркеры фибрилляции предсердий ации замен M235T, G-6A и G-217A в гене AGT с риском развития ФП [42]; позднее данный факт был подтвержден -аллель T и генотип T/T полиморфизма M235T, а также аллель G и генотип G/G полиморфизма G-6A продемонстрировали ассоциации с повышенным риском развития данной патологии [43,44]. В продолжение, в 2008 г., ýта же группа провела повторное исследование с привлечением большего количества пациентов (1 236 человек).…”