The association of stromal antigen 3 (STAG3) sequence variations with spermatogenic impairment in the male Korean population / 亚洲男科学杂志(英文版)

The stromal antigen 3 (STAG3) gene, encoding a meiosis-specific cohesin component, is a strong candidate for causing male infertility, but little is known about this gene so far. We identified STAG3 in patients with nonobstructive azoospermia (NOA) and normozoospermia in the Korean population. The coding regions and their intron boundaries of STAG3 were identified in 120 Korean men with spermatogenic impairments and 245 normal controls by using direct sequencing and haplotype analysis. A total of 30 sequence variations were identified in this study. Of the total, seven were exonic variants, 18 were intronic variants, one was in the 5'-UTR, and four were in the 3'-UTR. Pathogenic variations that directly caused NOA were not identified. However, two variants, c.3669+35C>G (rs1727130) and +198A>T (rs1052482), showed significant differences in the frequency between the patient and control groups (P = 0.021, odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.098-2.918) and were tightly linked in the linkage disequilibrium (LD) block. When pmir-rs1052482A was cotransfected with miR-3162-5p, there was a substantial decrease in luciferase activity, compared with pmir-rs1052482T. This result suggests that rs1052482 was located within a binding site of miR-3162-5p in the STAG3 3'-UTR, and the minor allele, the rs1052482T polymorphism, might offset inhibition by miR-3162-5p. We are the first to identify a total of 30 single-nucleotide variations (SNVs) of STAG3 gene in the Korean population. We found that two SNVs (rs1727130 and rs1052482) located in the 3'-UTR region may be associated with the NOA phenotype. Our findings contribute to understanding male infertility with spermatogenic impairment.

An overview of current knowledge about cell-free RNA in amniotic fluid

Cell-free nucleic acids (cf-NAs) originate in trophoblasts and are detected in the maternal plasma. Using innovative bioinformatic technologies such as next-generation sequencing, cf-NAs in the maternal plasma have been rapidly applied in prenatal genetic screening for fetal aneuploidy. Amniotic fluid is a complex and dynamic fluid that provides growth factors and protection to the fetus. In 2001, the presence of cf-NA in amniotic fluid was reported. Amniotic fluid is in direct contact with the fetus and is derived from fetal urine and maternal and fetal plasma. Therefore, these genetic materials have been suggested to reflect fetal health and provide real-time genetic information regarding fetal development. Recently, several studies evaluated the global gene expression changes of amniot ic fluid cell-free RNA according to gestational age. In addition, by analyzing the transcriptome in the amniotic fluid of fetal aneuploidy, potential key pathways and novel biomarkers for fetal chromosomal aneuploidy were identified. Here, we review the current knowledge of cell-free RNA in amniotic fluid and suggest future research directions.

Carrier screening for (CGG)n repeat expansion of FMR1 gene in Korean women

PURPOSE: We examined the prevalence and CGG/AGG repeat structure of expanded alleles of the FMR1 gene in preconceptional and pregnant Korean women. MATERIALS AND METHODS: The CGG repeats in the FMR1 genes of 1,408 women were analyzed by polymerase chain reaction and Southern blot analysis. To estimate the prevalence of expansion alleles, the individuals were divided into low risk and high risk group. RESULTS: Within this population, 98.4% had normal alleles and 1.6% had abnormal alleles including intermediate (0.6%), premutation (0.5%), full mutation (0.1%), and hemizygous (0.4%) alleles. There were 2 premutation alleles (1:666, 95% confidence interval [CI] 1:250-1,776) in the low risk group and 5 premutation alleles (1:15, 95% 1:6-36) in the high risk group. There were 8 intermediate alleles (1:167, 95% CI 1:130-213) in the low risk group and 1 intermediate alleles (1:76, 95% CI 1:11-533) in the high group. Six of the 7 premutation alleles did not contain AGG interruptions within the repeats and 1 had a single AGG interruption. Four of the 9 intermediate alleles contained 2-3 AGG, 4 had a single AGG, and 1 had no AGG interruptions. CONCLUSION: Our study demonstrates the prevalence and CGG/AGG structure of expansion alleles in Korean women. The identified premutation prevalence is higher than that of other Asian populations and lower than that of Caucasian populations. Although our study is limited by size and population bias, our findings could prove useful for genetic counseling of preconceptional or pregnant women.

Cardio-thoracic Ratio (CTR) for Detection of Left Ventricular Hypertrophy (LVH) in Elderly People

BACKGROUND: Left ventricular hypertrophy (LVH) is closely related with a high death rate, rhythmia, ischemic heart disease, stroke and sudden death. It is known that the prognosis becomes better as LVH regresses. Therefore, it is important to diagnose it correctly with ease in primary care. The authors evaluated the most standard cardio-thoracic ratio (CTR) with respect to LVH oriented towards elderly people whose body habitus changed over time as they had become older, and evaluated the factors which affect the rate of diagnosis including sensitivity and specificity. METHODS: A total of 231 subjects over 60 years of age who visited a general hospital health promotion center from March 1997 to August 2003, underwent echocardiography and identified not to have heart disease were selected. LV (left vetricular) mass was measured through echocardiography. LV mass was divided by 2.7 times of height (m) by Deveruex's method, and 49.1 g/m2.7 for men and 46.7 g/m2.7 for women were set to be standards of LVH. CTR was obtained by dividing the maximum transverse diameter of the heart by maximum transverse diameter of thorax on chest PA. RESULTS: CTR was observed on the basis of 0.45, 0.5, 0.55, and the agreement was highest of 0.5 for men and 0.45 for women. However, considering the sensitivity, the specificity, and the positive predictive value, it was thought to be most proper to be set at 0.5 was be standard for both men and women. When diagnosing LVH through chest PA, if 0.5 was set to be standard, false positive become high in women, false negative became high as height increased, and false negative became high as body mass index (BMI) increased. The smoking group showed higher false negative compared to the non- smoking group, and the false negative was higher as the level of hemoglobin increased. CONCLUSION: When diagnosing LVH through CTR in elderly people, it was appropriate to set 0.5 as a standard, but it is necessary to consider sex, body habitus, BMI, smoking and the level of hemoglobin.

Electrocardiogram as a Diagnostic Method for Left Ventricular Hypertrophy

BACKGROUND: The purpose of this study was to examine the sensitivity and specificity of ECG as a tool for detecting echocardiographically defined LVH in a population-based sample and to examine the impact of a variety of factors that affect the sensitivity and specificity of ECG for detection of LVH. METHODS: A total of 1,130 subjects who received a thorough medical checkup for cardiologic department voluntarily were selected. The subjects were examined using M-mode echocardiography and standard 12-lead ECG. The chi-square test was used to test for differences in sensitivity and specificity of ECG for echocardiographically defined LVH. Cochran-Mantel-Haenszel statistic was used to adjust for sex, age, and obesity and to test the association between cigarette smoking, amount of alcohol, exercise, hypertension, diabetes mellitus (DM) and sensitivity and specificity of ECG. RESULTS: Echocardiographic LVH was detected in 434 (38.4%) and electrocardiographic features of LVH were present in 146 (12.9%). ECG for diagnosis of LVH showed sensitivity of 20.0%, specificity of 91.5%, and diagnostic accuracy of 64.1%. Sensitivity of ECG for LVH was higher in persons with obesity (P=.04) or hypertension (P=.04). Specificity of ECG for LVH was lower in persons with hypertension (P=.003) CONCLUSION: ECG has a low sensitivity and a high specificity for echocardiographically defined LVH. Attention must be paid to carefully interpret ECG for diagnosis of LVH in persons with obesity or hypertension, because the rate of false positives and negatives can be increased.