Sudden Unexplained Nocturnal Death Syndrome Cases Research Articles

HCN4 Gene Variations in Sudden Unexplained Nocturnal Death Syndrome in the Southern Han Chinese Population.

Sudden unexplained nocturnal death syndrome (SUNDS) is widely considered to be related to hereditary fatal arrhythmias. Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) channels are widely distributed in sinus myocytes and play a profound role in generating pacemaker electro-activity in cardiomyocytes. In the present study, the potential correlation between HCN4 gene variations and the occurrence of SUNDS was investigated. Genomic DNA was extracted from blood samples of both 119 unrelated SUNDS patients and 184 healthy individuals and screened for candidate HCN4 gene variants. One missense heterozygous variant c.1578C>T (Ala195Val) and four synonymous heterozygous variants c.1552C>T, c.2833C>T, c.3823C>T, and c.4189C>A were discovered in the SUNDS cases. The missense variant c.1578C>T (Ala195Val) was absent in 163 recruited controls and 105 persons of the Southern Han Chinese population, had in-silico prediction indications as damaging, and was reported prevalent in sudden infant death, and is thus likely to be involved in SUNDS.

Sudden Unexplained Nocturnal Death Syndrome: Epidemiological and Morphological Characteristics in Thai Autopsy Cases.

With limited knowledge on epidemiological and morphological characteristics of sudden unexplained nocturnal death syndrome (SUNDS), this study was aimed to identify such data in Thai SUNDS autopsy cases. All the cases were men and nondrug abusers aged 20-49years old. Most cases were originated in the Northeastern region of Thailand. Half of them were found dead from midnight to 6 a.m., with a peak time at 2 a.m. The death rate was relatively higher in May and June. Most SUNDS cases were blue-collar workers (93.2%) and nonsmokers (60%), with a normal BMI (72.1%). Approximately one-fifth of the cases had detectable blood alcohol concentrations. Symptoms before death were respiratory difficulty, seizures, and urinary incontinence. Their mean heart weight was 329.8±35.1g. Their lungs (88.6%) had some degree of congestion. Acute pancreatitis was not found in these SUNDS cases, and approximately half (40.9%) of the cases had their gastric content <100mL.

A Case-Control Study of Sudden Unexplained Nocturnal Death Syndrome in the Southern Chinese Han Population

To study the epidemiological characteristics of sudden unexplained nocturnal death syndrome (SUNDS) in the southern Chinese Han population during 2007 to 2013, we gathered 879 SUNDS victims from Dongguan City and in the Longgang District in Shenzhen City as the case group then selected 879 all-cause death cases, adopting a 1:1 pair method, as the control group I and collected 8142 all-cause death cases from the Bao'an District in Shenzhen City as the control group II, simultaneously. Case information collected was statistically analyzed. The annual incidence of SUNDS is 1.02 and 2.23 per 100,000 person-years for Dongguan City and in the Longgang District, respectively. The number of male and female victims is drastically different, with a ratio of 13.92:1, whereas the incidence between the 2 sexes is significantly different (χ2 = 78.734, P < 0.01), with an odds ratio value of 11.32 (95% confidence interval, 5.75-22.28). The age of death of SUNDS cases ranges from 17 to 55 years with a median age of 35 years; furthermore, the difference of distribution of age of death between the SUNDS victims and the all-cause death population is significant (χ2 = 767.12, P < 0.001). The birthplace of SUNDS victims is distributed throughout 27 provinces of China, but the difference between the SUNDS victims and the all-cause death population is not significant (χ2 = 27.273, P > 0.05). The monthly incidence of SUNDS is relatively higher from March to June, whereas the difference of monthly distribution between SUNDS victims and all-cause death population is significant (χ2 = 9.869, P < 0.05), with an odds ratio value of 1.42 (95% confidence interval, 1.14-1.76). Although the majority of SUNDS occurred during midnight sleep, they were mostly discovered from 7 to 9 am once the inmates or spouses woke in the morning. A total of 97.74% of the SUNDS victims were blue-collar factory workers with a high-intensity labor and poor education background. This investigation confirmed the stability of epidemiological characteristics of SUNDS in South China and implicated that risk factors of this fatal disease still exist. The efficient strategy of early identification such as molecular diagnosis for SUNDS is extremely urgently required.

Association of common variants in NOS1AP gene with sudden unexplained nocturnal death syndrome in the southern Chinese Han population

Here, we investigate the association of common polymorphisms of the NOS1AP gene with sudden unexplained nocturnal death syndrome (SUNDS) in the southern Chinese Han population. We genetically screened five common NOS1AP polymorphisms (rs10918594, rs12143842, rs16847548, rs12567209, and rs10494366) previously reported to be associated with QT interval variation and sudden cardiac death (SCD) in 123 sporadic SUNDS cases and 166 healthy controls using polymerase chain reaction (PCR) and direct DNA sequencing. In the present study, the A allele of rs12567209 was more common in controls than in SUNDS cases, which was associated with 0.656-fold decreased risk of SUNDS (95% confidence interval 0.431 to 0.998, P = 0.048) compared with G allele. Under the dominant genetic model, GA + AA genotype of rs12567209 was also more common in controls than in SUNDS cases, which was associated with 0.604-fold decreased risk of SUNDS (95 % confidence interval 0.368 to 0.991, P = 0.045) compared with GG genotype. No significant associations of rs10918594, rs12143842, rs16847548, and rs10494366 with SUNDS were observed (P > 0.05). In haplotype analyses, the distribution of haplotype GCTA was significantly overrepresented in controls compared to SUNDS cases (P = 0.040). This is the first report of the association of common NOS1AP polymorphisms with SUNDS in the southern Chinese Han population. These findings suggest that the A allele of rs12567209 and haplotype GCTA may serve as a protective modifier.

Postmortem molecular analysis of KCNQ1, KCNH2, KCNE1 and KCNE2 genes in sudden unexplained nocturnal death syndrome in the Chinese Han population

The etiology of sudden unexplained nocturnal death syndrome (SUNDS) remains unclear. Previous studies have implicated that SUNDS is probably allelic to cardiac sodium channel diseases such as Brugada syndrome. The variation in cardiac potassium channels is the main genetic cause of inherited long QT syndrome (LQTS), which may manifest as syncope and sudden cardiac death without structural disease. We hypothesized that cardiac potassium channel disease may be responsible for certain Chinese SUNDS cases. Genotyping of 4 main LQTS-susceptibility genes (KCNQ1, KCNH2, KCNE1, and KCNE2) was performed here for the first time in SUNDS victims from the Chinese Han population to address the pathogenic cause of some SUNDS using polymerase chain reaction and direct DNA sequencing. 120 sporadic SUNDS cases were enrolled. Genomic DNA was extracted from blood samples. A total of 2 novel non-synonymous mutations and 3 previously reported arrhythmia susceptibility polymorphisms were identified in KCNQ1, KCNH2, KCNE1, and KCNE2. We concluded that the variants in KCNQ1, KCNH2, KCNE1 and KCNE2 genes may be correlated with the occurrence of part of SUNDS cases in southern China.