Absence of association between length variation of an intronic region in the NFATC1 gene and congenital heart defects in a Han Chinese population.

Congenital heart defects are complicated birth defects due to the interaction of genetic and environmental factors. Previous research indicated the importance of transcription factors in heart development, which suggested that mutations of transcription factor genes could be genetic determinants of congenital heart defects. Recently, the length variation of an intronic region in the NFATC1 gene was linked to ventricular septal defect (VSD). In this study, we detected the length variation of the region in a Han Chinese population of patients with nonsyndromic VSD, atrial septal defect, patent ductus arteriosus, and control individuals. We found a new allele of the length variation with four repeats of a 44-bp region. At the same time, all the alleles were found in both patient and control groups and there were no significant differences in genotype distribution between the patients and controls. The results suggested no association of the length variation of the intronic region in NFATC1 gene with VSD, atrial septal defect, and patent ductus arteriosus.

Enhanced prothrombin formation and platelet activation in Chinese patients after transcatheter closure of atrial septal defect.

BACKGROUND: The objective of this study was to investigate changes in coagulation activation and platelet activation after transcatheter closure of atrial septal defect (ASD) by determining the levels of specific markers over time to provide insight into preventing postprocedural embolism. HYPOTHESIS: We hypothesis that the activation status of coagulation and the platelet would be changed after the closure of ASD. METHODS: Forty consecutive patients who underwent transcatheter closure of ASD with the Lifetech ASD occluder (Lifetech Scientific, Shenzhen, China) were included in this prospective study. The serum level of prothrombin fragment 1 + 2 (F1 + 2) and expressions of P-selectin (CD62P) and platelet glycoprotein IIb/IIIa receptor (CD41a) on the surface of platelets were evaluated at baseline and at 1 day, 1 month, and 3 months after the closure. RESULTS: The median F1 + 2 level was 0.96 nmol/L. This increased to a maximal value of 1.43 nmol/L at 1 day after closure, but gradually returned to the baseline level at 1 month after closure and remained there at 3 months after closure (medians were 0.98 nmol/L and 1.08 nmol/L, respectively). Platelet surface expression of CD62P and CD41a decreased at 1 day, 1 month, and 3 months after closure. For CD62P, average expressions were 8.21% +/- 2.11%, 6.28% +/- 1.72%, 5.29% +/- 1.52%, and 4.41% +/- 1.11%, respectively, for baseline and 1 day, 1 month, and 3 months after closure. For CD41a, average expressions were 79.37% +/- 14.14%, 71.98% +/- 13.77, 56.69% +/- 13.05%, and 54.88% +/- 11.62%, respectively. CONCLUSIONS: Transcatheter closure of ASD with the Lifetech ASD occluder was associated with significantly increased coagulation activation and decreased platelet activation. No evidence supporting the use of aspirin to prevent thrombus formation after closure was found.

A novel mutation in GATA4 gene associated with dominant inherited familial atrial septal defect.

OBJECTIVE: Atrial septal defect (ASD) is a common congenital heart disease (CHD). Although most cases are sporadic, familial cases have been reported. The transcription factors NKX2.5 and GATA4 play important roles in the pathogenesis of ASD. Mutations in either gene have been identified in familial cases of ASD. Here, we examine a Chinese family with isolated ASD to find out whether there is any mutation in NKX2.5 or GATA4 accounting for the etiology. METHODS: We identified kindred spanning 3 generations in which 8 of 31 (38%) individuals had ASD. One hundred seventy unrelated individuals were included as controls. Peripheral blood samples were collected and genomic DNA was extracted from the leukocytes. NKX2.5 and GATA4 were amplified by polymerase chain reaction (PCR) with specific primers. The sequences of PCR products were compared between affected members and unaffected members, as well as controls. RESULTS: Direct sequencing of NKX2.5 from the genomic DNA of family members failed to identify mutations, whereas sequencing of GATA4 identified an A-to-G transition at nucleotide 928 in exon 5 that predicted a methionine to valine substitution at codon 310 (M310V) in the NLS region. All affected members and a patriarch of the family who was recognized as a carrier exhibited this mutation, whereas the other unaffected family members or control individuals did not. This mutation has not been reported previously in either familial or sporadic cases of CHD. CONCLUSIONS: We identified a novel M310V mutation in GATA4 gene that is located in the NLS region and leads to hereditary ASD in a Chinese family. In this family, we identified a carrier with incomplete penetrance and 8 patients with variable expressivity. However, the mechanism by which this mutation contributes to the development of a congenital heart defect remains to be ascertained.

Are birth defects among Hispanics related to maternal nativity or number of years lived in the United States?

BACKGROUND: Literature on the risk of birth defects among foreign- versus U.S.-born Hispanics is limited or inconsistent. We examined the association between country of birth, immigration patterns, and birth defects among Hispanic mothers. METHODS: We used data from the National Birth Defects Prevention Study and calculated odds ratios (ORs) and 95% confidence intervals and assessed the relationship between mothers' country of birth, years lived in the United States, and birth defects among 575 foreign-born compared to 539 U.S.-born Hispanic mothers. RESULTS: Hispanic mothers born in Mexico/Central America were more likely to deliver babies with spina bifida (OR = 1.53) than their U.S.-born counterparts. Also, mothers born in Mexico/Central America or who were recent United States immigrants (< or =5 years) were less likely to deliver babies with all atrial septal defects combined, all septal defects combined, or atrial septal defect, secundum type. However, Hispanic foreign-born mothers who lived in the United States for >5 years were more likely to deliver babies with all neural tube defects combined (OR = 1.42), spina bifida (OR = 1.89), and longitudinal limb defects (OR = 2.34). Foreign-born mothers, regardless of their number of years lived in the United States, were more likely to deliver babies with anotia or microtia. CONCLUSIONS: Depending on the type of birth defect, foreign-born Hispanic mothers might be at higher or lower risk of delivering babies with the defects. The differences might reflect variations in predisposition, cultural norms, behavioral characteristics, and/or ascertainment of the birth defects.

Patent foramen ovale and the risk of ischemic stroke in a multiethnic population.

OBJECTIVES: We sought to assess the risk of ischemic stroke from a patent foramen ovale (PFO) in the multiethnic prospective cohort of northern Manhattan. BACKGROUND: Patent foramen ovale has been associated with increased risk of ischemic stroke, mainly in case-control studies. The actual PFO-related stroke risk in the general population is unclear. METHODS: The presence of PFO was assessed at baseline by using transthoracic 2-dimensional echocardiography with contrast injection in 1,100 stroke-free subjects older than 39 years of age (mean age 68.7 +/- 10.0 years) from the Northern Manhattan Study (NOMAS). The presence of atrial septal aneurysm (ASA) also was recorded. Subjects were followed annually for outcomes. We assessed PFO/ASA-related stroke risk after adjusting for established stroke risk factors. RESULTS: We detected PFO in 164 subjects (14.9%); ASA was present in 27 subjects (2.5%) and associated with PFO in 19 subjects. During a mean follow-up of 79.7 +/- 28.0 months, an ischemic stroke occurred in 68 subjects (6.2%). After adjustment for demographics and risk factors, PFO was not found to be significantly associated with stroke (hazard ratio 1.64, 95% confidence interval [CI] 0.87 to 3.09). The same trend was observed in all age, gender, and race-ethnic subgroups. The coexistence of PFO and ASA did not increase the stroke risk (adjusted hazard ratio 1.25, 95% CI 0.17 to 9.24). Isolated ASA was associated with elevated stroke incidence (2 of 8, or 25%; adjusted hazard ratio 3.66, 95% CI 0.88 to 15.30). CONCLUSIONS: Patent foramen ovale, alone or together with ASA, was not associated with an increased stroke risk in this multiethnic cohort. The independent role of ASA needs further assessment in appositely designed and powered studies.

Race-ethnic differences in patent foramen ovale, atrial septal aneurysm, and right atrial anatomy among ischemic stroke patients.

BACKGROUND AND PURPOSE: Stroke remains a substantial cause of mortality and morbidity in the United States. Racial differences in stroke incidence and mortality persist with well-known excesses among blacks. Information on stroke among Hispanics is limited. In particular, little is known about whether patent foramen ovale (PFO), atrial septal aneurysm (ASA), and other atrial anomalies associated with cryptogenic stroke differ among minority populations. METHODS: As a part of the PFO in Cryptogenic Stroke Study, transesophageal echocardiography was performed in a cohort of 630 ischemic stroke patients (mean age, 59+/-12 years; 44% women; 45% whites, 35% blacks, 17% Hispanics, 3% other). The prevalences of PFO, ASA, and right atrial (RA) anatomy favoring paradoxical embolization were compared among race-ethnic groups. Statistical analyses used analysis of variance for continuous variables and logistic regression for dichotomous variables with adjustments for age and sex. RESULTS: Age- and sex-adjusted prevalences of PFO and ASA were similar across race-ethnic subgroups. However, large PFO was significantly less prevalent among blacks than among whites (odds ratio, 0.47; 95% confidence interval, 0.24 to 0.91; P=0.02). RA anatomy favoring paradoxical embolization was also significantly less prevalent among blacks compared with whites (odds ratio, 0.62; 95% confidence interval, 0.43 to 0.91; P=0.01). There were no significant differences in prevalence between whites and Hispanics. CONCLUSIONS: Although the frequency of PFO did not vary among race-ethnic groups, a large PFO and RA anatomy favoring paradoxical embolization were significantly more prevalent among whites and Hispanics compared with blacks. These may be relatively more important risk factors for stroke among whites and Hispanics than among blacks.

Racial differences in the prevalence of cardiac sources of embolism in subjects with unexplained stroke or transient ischemic attack evaluated by transesophageal echocardiography.

Little is known about the distribution of cardiac sources of embolism among African-Americans with cryptogenic cerebrovascular events. We compared the prevalence of potential cardiac sources of embolism between black and white patients referred to our laboratory for transesophageal echocardiographic (TEE) evaluation of unexplained stroke or transient ischemic attack. Records were reviewed to exclude subjects with high-risk cardiac or vascular disorders likely to explain the index event. Of 297 patients satisfying the inclusion criteria, 196 were white and 87 black. Potential cardioembolic sources were significantly less common in blacks than in whites (adjusted odds ratio [OR], 0.44; 95% confidence interval [CI] 0.26 to 0.75), and related largely to the difference in prevalence of interatrial communication (OR 0.40; 95% CI 0.21 to 0.74). In contrast, African-Americans had a higher prevalence of left ventricular (LV) hypertrophy (OR 3.50; 95% CI 1.97 to 6.22), and particularly, moderate or severe hypertrophy (OR 4.03; 95% CI 1.88 to 9.65) compared with whites. In conclusion, in African-Americans with unexplained cerebrovascular events, the yield of TEE for potential cardioembolic sources, and especially interatrial communication, is lower than in their white counterparts. African-Americans exhibit a substantially higher prevalence of LV hypertrophy, which may be a marker for a higher burden of subclinical cerebrovascular disease involved in the pathogenesis of cryptogenic cerebral ischemia in this population.

Prevalence of congenital cardiac anomalies at high altitude.

The effect of high altitude on the prevalence of congenital heart disease was tested by examining 1,116 school children at four study sites in the People's Republic of China. Sites ranged in altitude from sea level to 4,500 m above sea level. Children were screened by physical examination, and an echocardiogram and electrocardiogram were performed on each child suspected of having a cardiac anomaly. A high prevalence of patent ductus arteriosus and atrial septal defect was found at the three high altitude sites and the effect of altitude was progressive. Both anomalies were postulated to be the result of the lower atmospheric oxygen tension present at high altitude. Failure of lower oxygen tension to constrict the ductus is thought to be the mechanism in patent ductus arteriosus. It is theorized that the persistence of high pulmonary vascular resistance and high right heart pressures at high altitude inhibits early closure of the foramen ovale. Subsequent growth may result in stretching of the fossa ovalis and incompetence of the flap and may produce an atrial septal defect. The high prevalence of atrial septal defect in tetralogy of Fallot is cited as a possible analogy because right ventricular pressure is high and right ventricular compliance is low from birth.