Common genetic variation in circadian clock genes are associated with cardiovascular risk factors in an African American and Hispanic/Latino cohort

Abstract

Misalignment of the internal circadian time with external physical time due to environmental factors or due to genetic variantion in circadian clock genes has been associated with increased incidence of cardiovascular risk factors. Common genetic variation in circadian genes in the United States have been identified predominantly in European ancestry individuals. We therefore examined the association between circadian clock single nucleotide polymorphisms (SNPs) in Clock, Cry1, Cry2, Bmal1 and Per3 genes and cardiovascular risk factors in African Americans and Hispanic/Latinos. We analyzed 17 candidate circadian SNPs in 1,166 subjects who self-identified as African-American or Hispanic/Latino and were enrolled in the UIC Cohort of Patients, Family and Friends. We found significant differences in the minor allele frequencies between African American and Hispanic/Latino subjects. Our analyses also established ethnic-specific SNPs that are associated with cardiovascular risk factors. In Hispanic/Latinos, the rs6850524 in Clock was associated with increased risk for hypertension, meanwhile rs12649507, rs4864546, and rs4864548 reduced the risk, also rs8192440 ( Cry1 ) reduced the risk for type 2 diabetes. In African Americans, the Clock rs1801260 and rs6850524 were negatively associated with the presence of obesity; Bmal1 rs11022775 reduced the risk for dyslipidemia; and the Cry2 rs2292912 increased the risk for dyslipidemia and diabetes. Genetic variations in candidate circadian-clock genes are associated with risk factors for cardiovascular disease in African-Americans and Hispanic/Latinos. Our findings may help to improve cardiovascular risk assessment as well as better understand how circadian misalignment impacts cardiovascular risk in diverse populations.

The Association between Circadian Clock Gene Polymorphisms and Metabolic Syndrome: A Systematic Review and Meta-Analysis

“…Moreover, the importance of the rs1801260 polymorphism with MetS risk was observed in the Asian subgroup rather than in the Caucasian and Hispanic subgroups in stratified analysis. The C allele was an independent risk factor for potential insulin resistance in Asian patients with essential hypertension [ 31 ] and diabetes [ 36 ], while in Caucasian patients was positively associated with hypertension and coronary artery disease and negatively with obesity [ 27 , 37 , 38 ]. Monteleone et al [ 12 ] noted that the rs1801260 genotypes were not linked with obesity.…”

“…Although studies revealed a discrepancy in the association of CLOCK rs6850524 polymorphism and MetS risk factors, this meta-analysis observed no association. However, some studies found an increased risk for hypertension [ 37 ] and obesity [ 22 , 29 ] associated with rs6850524. Still, additional studies are needed to investigate the molecular mechanism involved.…”

Association of BMAL1 clock gene polymorphisms with fasting glucose in children

“…Several previous studies have shown that BMAL1 gene polymorphisms are associated with the risk of developing type 2 diabetes in adults. 13 – 15 However, studies have noted that BMAL1 gene polymorphisms are not associated with the occurrence of type 2 diabetes in Japanese 33 and African-American 34 cohorts. In contrast to the findings of our study, Pappa et al showed that rs7950226 polymorphism of BMAL1 gene is associated with susceptibility to gestational diabetes in Greek pregnant women.…”

An in silico approach for the identification of detrimental missense SNPs and their potential impacts on human CRY2 protein

“…Multiple studies have revealed the involvement of single nucleotide polymorphisms (SNPs) in the human Cry2 gene (hCry2) with prostate and breast cancer [20], Non-Hodgkin's lymphoma [21], hepatocellular carcinoma [22]. CRY2 gene polymorphism has also been shown to be associated with bipolar disorder [23], [24], depression [25], [26], attention-de cit/hyperactivity disorder (ADHD) [27], dysthymia [28], osteoporosis [29], diabetes [30]- [32], cardiovascular disorders [33], elevated blood pressure and hypertension, elevated triglyceride levels [34], dyslipidemia [30] and the more obvious, sleep disorder [35] as well as affective disorders [36].…”