RESUMEN
BACKGROUND: Researchers have determined that Indians face a higher risk of heart disease, despite the fact that nearly half of them are vegetarians and lack many of the other traditional risk factors. In the below-30 age group, coronary artery disease mortality among Indians is three-fold higher than in the whites in United Kingdom and ten-fold higher than the Chinese in Singapore. High levels of homocysteine have been widely linked to the early onset of heart diseases in other populations, although a definite proof among Indians is lacking, which needs to be investigated by way of screening for factors responsible for high homocysteine levels. OBJECTIVE: To screen for genetic factors responsible for hyperhomocysteinemia and the risk for premature coronary artery disease. MATERIALS AND METHODS: A total of 100 individuals with proven premature coronary artery disease and 200 age-and-sex matched controls were screened for polymorphisms in Methylenetetrahydrofolate reductase (MTHFR) (C677T) Methionine synthase (MS) genes (A2756G, C2758G), and the B12 and Folate levels were estimated. RESULTS: Results from the mutational analysis revealed that in the study group, seven individuals had a polymorphism for the C677T allele in the MTHFR gene (one homozygous and six heterozygous) (Fischer's Exact test P > 0.046) (OR: 0.2711 95% CI 0.0774 to 0.9491). Six were heterozygous for the A2756G polymorphism in the MS gene (Fischer's Exact test P > 0.0012). None showed a polymorphism at the C2758G allele in the MS gene. Four controls showed heterozygosity for the C677T polymorphism and none for the MS gene. The B12 and Folate levels were significantly lower in the study group as compared to the controls. CONCLUSIONS: It is important to know which factors determine the total homocysteine concentrations. In the general population, the most important modifiable determinants of tHcy are folate intake and coffee consumption. Smoking and alcohol consumption are also associated with the total homocysteine concentrations, but more research is necessary to elucidate whether these relations are not originating from residual confounding due to other lifestyle factors.
RESUMEN
OBJECTIVE: To determine the prevalence of inhibin alpha gene variants in Indian women with premature ovarian failure. DESIGN: Mutational analysis of DNA from patients and control subjects. SETTING: Clinical genetics and molecular cytogenetic laboratory. PATIENTS(S): One hundred 46,XX women with premature ovarian failure and 50 healthy control subjects <40 years old. INTERVENTION(S): Blood samples were collected. MAIN OUTCOME MEASURE(S): Extraction of DNA from blood samples, amplification of inhibin alpha gene, restriction fragment length polymorphism (RFLP), and direct DNA sequencing. RESULT(S): The RFLP analysis revealed a 769G-->A missense inhibin alpha mutation. There were three inhibin alpha gene sequence variants that resulted in a change from 734 C-->A/Ala 245 Asp, 755 C-->A/Pro 252 His, and 777 C-->A/His 259 Gln by DNA sequencing. CONCLUSION(S): Variants in the inhibin alpha gene are strongly associated with premature ovarian failure in Indian patients.
