Background: Adiponectin is involved in regulating both glucose and fatty acid. Associations of the known adiponectin receptors 1 (ADIPOR1) single nucleotide polymorphism (SNP) with diabetes have been demonstrated while hypertriglyceridemia is frequently associated with cerebrovascular disease (CVD) among diabetes. Triglyceride metabolism was also reported to be different between genders and estrogen was observed to interfere with adiponectin effects via ADIPOR1. It seems important to investigate whether the ADIPOR1 SNP variants may be significant determinants in triglyceride metabolism and hence be a risk of CVD in specific gender. Methods: A survey was performed on random self-reported healthy subjects aged 35 and above with their biochemical data collected. Genotyping for ADIPOR1 SNP (rs1342387) was carried out using TaqMan Genotyping Assays. Interviews were also conducted regarding stress, adverse diet behavior and exercise. Multivariable logistic regression analyses were performed to identify the strongest contributing variables. Findings: The ADIPOR1 minor allele carrier (T/T and T/C) had significantly ( p = 0.02) higher TG mean compared to homozygous (C/C) major alleles. TG difference was significantly higher in male ( p = 0.02) with a larger difference in mean, whereas the difference disappeared among female ( p = 0.32). Multivariate logistic regression analyses were performed by defining abnormal TG based on NCEP criteria of metabolic syndrome, and when all life style variables were entered in the model with ADIPOR1, only the ADIPOR1 inmale showed significant ( p = 0.03) and very high association with abnormal TG (Exp( β ) 16.31). Discussion: The findings provide sample evidence of a relation between ADIPOR1 SNP minor allele carrier and high TG concentrations in male. The association of abnormal TG and ADIPOR1 is much stronger than that compared to life style. The implications of this survey may be further extend to identifying the genetic risk of abnormal TG at young age and reduce the CVD incidence by early intervention.
Hypertriglyceridemia is frequently associated with type 2 diabetes mellitus [
Given the studies regarding differences in TG metabolism between male and fenale [
Because we were unaware of any previous study of this nature, the present study was designed to investigate the capacity of using ADIPOR1 SNP to identify unacknowledged metabolic abnormality among healthy subjects and across gender.
The epidemiologic study of this preliminary investigation was conducted in Taiwan and performed on random subjects aged 35 and above who claimed to be healthy and under no medication. This study was approved by the Show-Chwan Memorial Hospital IRB board (IRB: #1020602) and had been carried out in accordance with the principles of the Declaration of Helsinki as revised in 2008. Blood pressure was measured sitting, after a minimum rest of 5 minutes and values were averaged by three different measurements separated by 2 minutes from each other. Concentrations of plasma glucose, TG, cholesterol, high density lipoprotein and low density lipoprotein were determined after an overnight (12-hour) fast.
ADIPOR1 SNP variant (rs1342387) locates on chromosome 1 and code for mRNA (NM_001290553.1) intron region (http://www.ncbi.nlm.nih.gov/snp), was reported by Mather et al. to have the most statistically significant association of increased diabetes incidence (p-value = 0.005) for minor allele carriers [
A total of 116 individuals, 67 females and 49 males were enrolled. The ADIPOR1 SNP allele frequency assessment satisfied the Hardy-Weinberg equilibrium [
A structured interview was also conducted by trained nurses regarding stress, adverse diet behavior (http://health99.hpa.gov.tw/OnlinkHealth/OnlinkHealth_list.aspx) and exercise (http://www.hpa.gov.tw/BHPNet/Web/Easy/FormCenterShow.aspx?No=201201130001) according to the questionnaire provided by Health Promotion Administration in Taiwan. In order to ascertain the genetic variants and life styles that contribute to lipid metabolism, we performed multivariable logistic regression analysis (adjusting for ADIPOR1, stress, adverse diet behavior and exercise) to identify the strongest contributing variables. TG was categorized into abnormal (TG ≥ 8.33 mmol/L) according to the guidelines by the National Cholesterol Education Program (NCEP) for metabolic syndrome. The relative odds ratios (OR) were expressed as exponentiation of the ß coefficient (Exp(ß)) with a p-value. The OR was obtained for total samples, males and females. Statistical analyses were performed using SPSS software, where two-tailed and p-values < 0.05 were considered statistically significant.
The study population was further divided on the basis of gender, and the comparison between genetic variants among each gender is detailed in
The data, collected based on a random population who were presumed to be healthy and with no medical history, indicated that male naturally showed a significantly higher association between ADIPOR1 variants and TG compared to female. When life style variables were entered in the multivariate model with ADIPOR1, ADIPOR 1 in male showed a significant and very high association with abnormal TG (Exp(ß) = 16.31, p = 0.03).
Based on the DPP population, Mather discovered that many of the adiponectin SNPs were associated with adiponectin concentration but none with diabetes incidence. ADIPOR1 SNP (rs1342387) had the most significant association with diabetes incidence, however, with ratio of only 1.18 [
Mather et al. also found that non-genetic factors were more potent determinant in adiponectin concentration using multivariable analysis [
In conclusion, disease is often defined and risk calculated by various biochemical abnormality. Hypertriglyceridemia is a significant risk factor for both ischemic stroke [
ADIPOR1 | ||||
---|---|---|---|---|
C/C | T/T, T/C | |||
N = 45 | N = 71 | |||
Mean ± SD | Mean ± SD | t-value/χ2 | p-value | |
SBP (mmHg) | 124 ± 16 | 121 ± 16 | 0.71 | 0.48 |
DBP (mmHg) | 77 ± 11 | 75 ± 11 | 0.62 | 0.54 |
Chol (mmol/L) | 10.49 ± 1.83 | 10.77 ± 1.78 | −0.83 | 0.41 |
TG (mmol/L) | 5.27 ± 2.66 | 6.77 ± 3.89 | −2.47 | 0.02* |
HDL (mmol/L) | 3.44 ± 0.94 | 3.33 ± 0.89 | 0.54 | 0.59 |
LDL (mmol/L) | 6.60 ± 1.78 | 6.83 ± 1.78 | −0.65 | 0.52 |
AC Sugar (mmol/L) | 5.27 ± 1.28 | 5.16 ± 0.78 | 0.80 | 0.43 |
HbA1C (%) | 5.66 ± 0.7 | 5.6 ± 0.57 | 0.49 | 0.63 |
Age | 46 ± 12 | 36 ± 73 | 0.83 | 0.41 |
Male† | 41% | 43% | 0.05 | 0.82 |
*Statistical significance p < 0.05; †Chi-square test.
Male | Female | |||||||
---|---|---|---|---|---|---|---|---|
C/C | T/T, C/T | t-value | p-value | C/C | T/T, C/T | t-value | p-value | |
Mean ± SD | Mean ± SD | Mean ± SD | Mean ± SD | |||||
Age | 47 ± 13 | 47 ± 13 | 0.17 | 0.87 | 46 ± 10 | 29 ± 30 | 0.87 | 0.39 |
SBP (mmHg) | 133 ± 17 | 126 ± 17 | 1.29 | 0.21 | 117 ± 12 | 117 ± 15 | 0.01 | 0.99 |
DBP (mmHg) | 82 ± 9 | 78 ± 10 | 1.60 | 0.12 | 72 ± 10 | 74 ± 12 | −0.52 | 0.60 |
Chol (mmol/L) | 10.55 ± 1.78 | 11.04 ± 1.89 | −0.95 | 0.35 | 10.43 ± 2.00 | 10.60 ± 0.72 | −0.28 | 0.78 |
TG (mmol/L) | 5.55 ± 1.89 | 7.94 ± 4.77 | −2.45 | 0.02* | 5.16 ± 3.16 | 5.88 ± 2.89 | −1.00 | 0.32 |
HDL (mmol/L) | 3.00 ± 0.83 | 2.83 ± 0.67 | 0.71 | 0.48 | 3.66 ± 0.89 | 3.66 ± 0.89 | −0.03 | 0.97 |
LDL (mmol/L) | 7.10 ± 1.78 | 7.49 ± 1.78 | −0.79 | 0.43 | 6.33 ± 1.78 | 6.33 ± 1.55 | −0.087 | 0.93 |
AC Sugar (mmol/L) | 5.11 ± 0.56 | 5.33 ± 1 | −0.73 | 0.47 | 5.44 ± 1.61 | 5.00 ± 0.50 | 1.24 | 0.23 |
HbA1C (%) | 5.88 ± 0.81 | 5.68 ± 0.80 | 0.85 | 0.40 | 5.52 ± 0.60 | 5.54 ± 0.30 | −0.17 | 0.87 |
*Statistical significance p < 0.05.
Total | Male | Female | |||||||
---|---|---|---|---|---|---|---|---|---|
Exp (ß) | Wald | p-value | Exp (ß) | Wald | p-value | Exp (ß) | Wald | p-value | |
ADIPOR1 | 4.28 | 5.91 | 0.02* | 16.31 | 4.86 | 0.03* | 2.42 | 1.44 | 0.23 |
Stress score | 0.89 | 1.40 | 0.24 | 0.77 | 2.53 | 0.11 | 0.99 | 0.02 | 0.90 |
Diet behavior score | 1.00 | 0.01 | 0.93 | 1.03 | 0.19 | 0.66 | 0.96 | 0.45 | 0.50 |
Exercise score | 1.00 | 0.00 | 0.98 | 1.00 | 0.40 | 0.53 | 1.00 | 0.08 | 0.77 |
*Statistical significance p < 0.05.
*Corresponding author.
This study was supported by Professor K. D. Yang’s research team and we also acknowledged the editorial assistance from Nigel Daly, Senior Editor of Asia Training Solutions Incorporation.
William C. W.Huang,Rong-FuChen,Yu-YingYang, (2015) Adiponectin Receptor 1 Single Nucleotide Polymorphism Is Highly Associated with Hypertriglyceridemia in Asian Male—A Novel Genetic Screening to Reduce Risk of Cerebrovascular Disease. World Journal of Neuroscience,05,323-327. doi: 10.4236/wjns.2015.55029