Assessment of cardiovascular disease risk factors in a genetically homogenous population of Parsi Zoroastrians in the United States: A pilot study

Objective Genetically isolated and homogenous populations are ideal for detecting genes underlying common complex diseases. The use of isolated populations with reduced disease heterogeneity has led to significant gene discoveries in the past. The aim of this pilot study was to assess the prevalence of cardiovascular disease (CVD) risk phenotypes in a genetically homogenous population of Parsi Zoroastrians in the United States. Methods Anthropometrics, blood pressure, and medical history were collected from 152 men and 186 women participating in a pilot study as part of the Parsi Family Study. The relative pairs used in the study included 60 parent–off springs, 28 siblings, 6 grandparent–grandchild, 7 avuncular, 18 half-siblings, 7 half-avuncular, and one half-first cousin. Estimates of genetic and environmental influence were calculated using a maximum likelihood-based variance components method implemented in SOLAR. Results The prevalence of overweight/obesity in adults (62%) was on par with current US prevalence. Hypertension and prehypertension were prevalent in 16% and 46% of the participants, respectively. The quantitative genetic analysis revealed significant heritabilities for all anthropometric phenotypes (P \u3c 0.05). Significant phenotypic correlations were found between blood pressure and anthropometric phenotypes (P \u3c 0.001), whereas significant genetic correlation was found for only diastolic blood pressure and fat free mass (rhoG = −0.88, P \u3c 0.05). Conclusion These preliminary data show significant additive genetic effects on CVD-related phenotypes in this population. Our findings represent the first epidemiological data in Parsi Zoroastrians in the United States and offer excellent promise for future genetic studies in this population. Am. J. Hum. Biol. 28:440–443, 2016. © 2016 Wiley Periodicals, Inc

Retinoic Acid Induces Expression of the Thyroid Hormone Transporter, Monocarboxylate Transporter 8 (Mct8)*

Retinoic acid (RA) and thyroid hormone are critical for differentiation and organogenesis in the embryo. Mct8 (monocarboxylate transporter 8), expressed predominantly in the brain and placenta, mediates thyroid hormone uptake from the circulation and is required for normal neural development. RA induces differentiation of F9 mouse teratocarcinoma cells toward neurons as well as extraembryonal endoderm. We hypothesized that Mct8 is functionally expressed in F9 cells and induced by RA. All-trans-RA (tRA) and other RA receptor (RAR) agonists dramatically (>300-fold) induced Mct8. tRA treatment significantly increased uptake of triiodothyronine and thyroxine (4.1- and 4.3-fold, respectively), which was abolished by a selective Mct8 inhibitor, bromosulfophthalein. Sequence inspection of the Mct8 promoter region and 5′-rapid amplification of cDNA ends PCR analysis in F9 cells identified 11 transcription start sites and a proximal Sp1 site but no TATA box. tRA significantly enhanced Mct8 promoter activity through a consensus RA-responsive element located 6.6 kilobases upstream of the coding region. A chromatin immunoprecipitation assay demonstrated binding of RAR and retinoid X receptor to the RA response element. The promotion of thyroid hormone uptake through the transcriptional up-regulation of Mct8 by RAR is likely to be important for extraembryonic endoderm development and neural differentiation. This finding demonstrates cross-talk between RA signaling and thyroid hormone signaling in early development at the level of the thyroid hormone transporter