Interaction between Vitamin D-Related Genetic Risk Score and Carbohydrate Intake on Body Fat Composition: A Study in Southeast Asian Minangkabau Women.

Metabolic diseases have been shown to be associated with low vitamin D status; however, the findings have been inconsistent. Hence, the objective of our study was to investigate the relationship between vitamin D status and metabolic disease-related traits in healthy Southeast Asian women and examine whether this relationship was modified by dietary factors using a nutrigenetic study. The study included 110 Minangkabau women (age: 25-60 years) from Padang, Indonesia. Genetic risk scores (GRS) were constructed based on five vitamin D-related single nucleotide polymorphisms (SNPs) (vitamin D-GRS) and ten metabolic disease-associated SNPs (metabolic-GRS). The metabolic-GRS was significantly associated with lower 25-hydroxyvitamin D (25(OH)D) concentrations (p = 0.009) and higher body mass index (BMI) (p = 0.016). Even though the vitamin D-GRS had no effect on metabolic traits (p > 0.12), an interaction was observed between the vitamin D-GRS and carbohydrate intake (g) on body fat percentage (BFP) (pinteraction = 0.049), where those individuals who consumed a high carbohydrate diet (mean ± SD: 319 g/d ± 46) and carried >2 vitamin D-lowering risk alleles had significantly higher BFP (p = 0.016). In summary, we have replicated the association of metabolic-GRS with higher BMI and lower 25(OH)D concentrations and identified a novel interaction between vitamin D-GRS and carbohydrate intake on body fat composition.

BRCA1 Promoter Methylation and Clinicopathological Characteristics in Sporadic Breast Cancer Patients in Indonesia

Objective: The aim of this study was to investigate the BRCA1 promoter methylation and clinicopathological characteristics in sporadic breast cancer patients in Indonesia. Methods: In this cohort study, we selected 90 patients with stage I-III who had definitive surgery at our institution in 2011-2014. Demographic and clinical data regarding pathological stage, breast cancer treatment, outcome etc. were collected from the medical records. Twelve patients had incomplete information on follow up and 18 samples had insufficient tissues for the experiment. Sixty patients with adequate cancer tissues and complete follow up record were analyzed, only 56 patients were analyzed because 4 samples mRNA expression could not be detected. The Mann­Whitney U tests for non-normally distributed groups were used to compare the levels expression of BRCA1 mRNA between methylated and non-methylated samples. Chi-square tests were used to compare methylation status, BRCA1 mRNA expression and clinicopathological characteristics. P value < 0.05 was considered as statistically significant correlation. Data analysis was held by using the GraphPad PRISM 7 (GraphPad Software Inc., USA). Results: DNA and RNA were isolated from primary tumor tissues of 56 breast cancer patients. BRCA1 promoter methylation was detected in 48 of 56 patients (85%). Level of BRCA1 mRNA expression was associated with decreased methylation level in the BRCA1 promoter regions suggesting the role of epigenetic silencing. However, there was no statistically significant association among methylation levels, BRCA1 mRNA transcript level with clinicopathological factors. Conclusion: To our knowledge, this is the first study investigating methylation status and level of BRCA1 mRNA transcripts among breast cancer patients in Indonesia. We found that the prevalence of BRCA1 promoter methylation is higher than other studies from different populations. However, further investigation involving larger number of patients is required.