Randall Beck and Michael J. Larson, Psychology and Neuroscience
Polymorphisms in the GR gene are an interesting and important area of research as these polymorphisms may be associated with an attenuated ability to cope with stress. This project bridged an unexplored gap between cellular and environmental stress and the expression of the GR gene—specifically the Bcl1 polymorphism of the GR gene. Cellular stress is any damage caused to the cell that alters its ability to function properly (Milisav, 2011). The Bcl1 polymorphism has what are known as C and G alleles that are genotyped as either homozygous GG, homozygous CC, or heterozygous CG (Srivastava et al., 2011). The homozygous GG polymorphism may be associated with hypersensitivity to stress hormones in the protein that is expressed through variations in the GR gene, the glucocorticoid receptor. The glucocorticoid receptor is responsible for the processing of glucocorticoids within the cell, primarily, cortisol. A hypersensitivity to glucocorticoids results in a delayed function of the glucocorticoid receptor (Chrousos & Gold, 2013), resulting in a buildup of cortisol within the cell leading to cellular damage. For our study we used telomere length as an indicator of cellular stress. Studies suggest that telomere length is associated with cellular stress, specifically that shorter telomeres indicate a greater degree of stress in the cell (Epel, 2004). Telomeres are proteins positioned at the ends of each chromatid and protect the cell’s DNA.
Environmental stress is caused by occurrences in our surroundings, such as noise, crowding, or natural disasters (Stokols & Altman, 1987). When our bodies experience environmental stress, cortisol is released into our cells. If the cells are not capable of processing that cortisol, this in turn will lead to an increased susceptibility to environmental stress, creating an unhealthy cycle of stress. The homozygous GG polymorphisms of the GR gene increase hypersensitivity of the glucocorticoid receptor. We specifically hypothesized that individuals with the homozygous GG allele combination on the Bcl1 polymorphism of the glucocorticoid receptor gene would be more susceptible to cellular and environmental stress than those with the C allele (homozygous or heterozygous).
Method and Results
We analyzed data from a study that collected genetic and cognitive data from 129 older adults between the ages of 49 and 85. Participants completed measures for demographic and health information as well as the Depression, Anxiety, and Stress Scale (DASS) (a measure of environmental and personal stress) and provided a saliva sample that was used for telomere analysis (a measure of cellular stress). The DASS is a set of three self-report scales designed to measure, define, and understand the negative emotional states of depression, anxiety and stress. Each scale consists of 14 items, divided into subscales of 2-5 items with similar content. For telomere and genetic analyses, the saliva was collected from each participant using DNA Genotek. The DNA was then isolated using the Qiagen QIAamp DNA Mini Kit. Telomere length was determined using qPCR analysis according to the protocol by O’Callaghan et al, 2008. Data were analyzed in three steps: 1) frequencies of allele groups and whether groups differ by sex using chi-square, 2) descriptive statistics; including means and standard deviations as a function of GR groups, 3) one-way ANOVAs to compare telomere length and DASS scores by allele groups.
In analyzing frequencies of allele groups, 46 people had the homozygous CC allele, 62 the heterozygous CG or GC, and 17 the homozygous GG allele. When the CC and CG were collapsed there were 108 with a C allele and 17 with only the homozygous GG allele. Males and females did not differ in the relative proportion represented by the C or GG alleles. Specifically, there were 57 females (85.1%) and 51 males (87.9%) with the C allele and 10 females (15.4%) and 7 males (12.1%) with the GG homozygous alleles. The chi-square statistic was not significant, indicating the proportions of males and females weren’t different by group (chi-square=.22, p=.64).
Our findings using descriptive statistics included 60 males and 69 females (mean age: 70.65 years, SD=7.86). The mean telomere length was 132.51 kb (SD=134.60). The DASS score mean was 12.29 (SD=11.71) with individual means of 3.20 (SD=4.23), 3.47 (SD=3.71), and 5.61 (SD=5.61) for the depression, anxiety, and stress subscales, respectively. Telomere data were missing for 19 participants and four were missing GR allele data due to insufficient saliva concentrations.
In using the one-way ANOVAs to compare telomere length and DASS scores by allele groups we found that there were no significant differences between C and GG allele carriers for telomere length (kb). The overall DASS score was not significantly different between groups, F(1,106)=2.17, p=.14, and its subscales of anxiety and stress were also not significantly different between groups, F(1,106)=1.40,p=.24, and F(1,106)=.49, p = .48, respectively. Notably, however, the depression subscale of the DASS was different between the allele groups, F(1,106)=4.45, p = .04, with slightly higher depression scores for those with the GG allele (mean = 5.06 SD = 6.70) than those with a C allele (mean = 2.80, SD = 3.56).
Summary and Conclusion
Overall, our results showed that there were no differences in allele frequency between sexes. Similarly, there were no differences in telomere length, stress score, anxiety score, or overall DASS score between groups. However, the depression subscale of the DASS was different between allele groups. Our results show that those with the GG allele scored slightly higher than those with the C allele, indicating that a greater degree of depressive symptoms by those with the GG allele. Some limitations apply such as the low number of participants with the GG allele (17), those whose telomere information was missing (19) and those with insufficient saliva concentrations (4). The difference in DASS scores, specifically in the depression subgroup, is a notable finding and deserves the attention of future studies in the endeavor to better understand the connection between the GG allele and the role it plays in cellular and environmental stress.
- Chrousos, G., & Gold, P. (2012, July 1). A healthy body in a healthy mind-and vice versa-the damaging power of “uncontrollable” stress. The Journal of Clinical Endocrinology & Metabolism. Retrieved October 20, 2014 from http://press.endocrine.org/doi/full/10/1210/jcem.83.6.4908
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- Epel, E. (2004). From The Cover: Accelerated Telomere Shortening In Response To Life Stress. Proceedings of the National Academy of Sciences, 17312-17315.
- Milisav, I. (2011, November 21). Cellular stress response. Retrieved October 5, 2015, from http://cdn.intechopen.com/pdfs/23657/InTech-Cellular_stress_responses.pdf
- Srivastava, N., Prakash, J., Lakhan, R., Agarwal, C., Pant, D., & Mittal, B. (2011). Influence of Bcl-1 Gene Polymorphism of Glucocorticoid Receptor Gene (NR3C1, rs41423247) on Blood Pressure, Glucose in Northern Indians. Indian Journal of Clinical Biochemistry, 125-130.
- Stokols, D., & Altman, I. (1987). Handbook of environmental psychology. New York: Wiley. 578-580
- O’callaghan, N., Dhillon, V., Thomas, P., & Fenech, M. (2008). A quantitative real-time PCR method for absolute telomere length. Biotechniques, 807-809.