The Variant rs1784042 of the SIDT2 Gene is Associated with Metabolic Syndrome through Low HDL-c Levels in a Mexican Population
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Demographic, Anthropometric and Clinical Measurements
2.3. Sample Genotyping and Selection of SNPs for Validation
2.3.1. Discovery Phase
2.3.2. Replication Phase
2.4. Statistical Power of the Study
2.5. Conditional and Haplotype Association Analysis
2.6. Statistical Analysis
3. Results
3.1. Demographic Data of the Study Population
3.2. Prevalence of MetS and Its Components by Gender and Age Groups
3.3. Association Analyses of Genetic Variants rs17120425 and rs1784042 of SIDT2 with MetS
3.4. Conditional Analysis of SIDT2 Locus
3.5. Haplotype Association Analysis
3.6. In Silico Functional Analysis of Genetic Variants rs17120425 and rs1784042 in SIDT2
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Publisher’s Note
References
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Parameter | Total Sample | Men | Women | p Value |
---|---|---|---|---|
n = 1963 | n = 593 | n = 1370 | ||
Age(years) 1 | 52.0 (40.0–62.0) | 46.0 (36.0–57.0) | 54.0 (43.0–63.0) | <0.001 |
Body mass index (kg/m2) 1 | 26.7 (24.0–29.7) | 26.5 (24.1–29.0) | 26.8 (24.0–30.1) | 0.133 |
Overweight 2 | 42.9 (40.7–45.0) | 48.8 (44.9–52.8) | 40.2 (37.7–42.8) | <0.001 |
Obesity 2 | 23.9 (22.0–25.8) | 19.6 (16.5–22.8) | 25.7 (23.4–28.0) | 0.003 |
Waist circumference (cm) 1 | 94.0 (86.0–101.0) | 96.0 (90.0–102.0) | 92.0 (85–100.0) | <0.001 |
Body fat proportion 1 | 41.9 (34.0–47.2) | 31.5 (27.7–34.7) | 45.1 (40.7–49.1) | <0.001 |
Leisure time physical activity (hour/week) 1 | 1.5 (0.3–3.5) | 1.7 (0.4–5.0) | 1.1 (0.2–3.5) | <0.001 |
Active (>150 min/week) 2 | 34.9 (32.8–37.0) | 36.6 (32.8–40.4) | 28.2 (25.8–30.6) | <0.001 |
Smoking current 2 | 12.3 (10.9–13.7) | 21.3 (18.0–26.6) | 9.0 (7.5–10.6) | <0.001 |
Smoking past 2 | 27.5 (25.5–29.4) | 39.7 (35.7–43.6) | 23.8 (21.5–26.1) | <0.001 |
Systolic blood pressure (mmHg) 1 | 118.0 (108.0–129.5) | 122.0 (113.0–131.0) | 116.0 (106.0–129.0) | <0.001 |
Diastolic blood pressure (mmHg) 1 | 74.0 (68.0–81.0) | 77.0 (70–84) | 73.0 (66.0–79.0) | <0.001 |
Fasting plasma glucose (mg/dL) 1 | 97.0 (90.0–106.0) | 98.0 (92–107) | 96.0 (90.0–104.0) | <0.001 |
Total cholesterol (mg/dL) 1 | 140.6 (85.4–213.6) | 167.0 (105.0–266.0) | 128.0 (83.0–193.0) | <0.001 |
Low density lipoprotein-c (mg/dL) 1,3 | 120.0 (98.0–145.4) | 116.0 (97–143.0) | 121.0 (99.0–147.0) | 0.009 |
High density lipoprotein-c (mg/dL) 1,4 | 44.0 (37.0–52.0) | 39.0 (34.0–46.0) | 46.0 (39.0–54.0) | <0.001 |
Metabolic Syndrome 2,5 | 52.6 (50.4–54.8) | 45.7 (41.6–49.7) | 55.6 (52.9–58.3) | <0.001 |
Triglycerides (mg/dL) 1 | 156.0 (112.0–209.0) | 168.0 (118.0–247.0) | 151.0 (109.0–199.0) | <0.001 |
Total | Men | Women | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Outcome | Genotype | Control, n (%) | Case, n (%) | OR 1,7 (95% CI) | p Value | Control, n (%) | Case, n (%) | OR 2 (95% CI) | p Value | Control, n (%) | Case, n (%) | OR 2 (95% CI) | p Value |
MetS 3 | GG | 742 (80.2) | 858 (83.3) | Ref. | 256 (80.3) | 232 (86.3) | Ref. | 486 (80.2) | 626 (82.4) | Ref. | |||
GA | 173 (18.8) | 160(15.5) | 0.79 (0.61–1.01) | 0.065 | 58 (18.2) | 36 (13.4) | 0.66 (0.41–1.05) | 0.078 | 115 (19.0) | 124 (16.3) | 0.86 (0.63–1.15) | 0.307 | |
AA | 10 (1.0) | 11 (1.1) | 0.83 (0.33–2.10) | 0.700 | 5 (1.6) | 1 (0.4) | 0.15 (0.02–1.39) | 0.095 | 5 (0.8) | 10 (1.3) | 1.59 (0.48–5.35) | 0.450 | |
Additive model | 0.82 (0.65–1.02) | 0.074 | 0.60 (0.39–0.92) | 0.018 | 0.93 (0.71–1.21) | 0.575 | |||||||
Low HDL- cholesterol 4 | GG | 514 (76.4) | 1086 (84.8) | Ref. | 203 (79.9) | 285 (85.3) | Ref. | 311 (74.2) | 801 (84.6) | Ref. | |||
GA | 151 (22.4) | 182 (14.2) | 0.54 (0.42–0.69) | 7.5 × 10−7 | 48 (18.9) | 46 (13.8) | 0.65 (0.42–1.02) | 0.059 | 103 (24.6) | 136 (14.4) | 0.50 (0.37–0.66) | 2.7 × 10−6 | |
AA | 8 (1.2) | 13 (1.0) | 0.73 (0.30–1.79) | 0.492 | 3 (1.2) | 3 (0.9) | 0.66 (0.13–3.32) | 0.613 | 5 (1.2) | 10 (1.1) | 0.78 (0.26–2.31) | 0.652 | |
Additive model | 0.60 (0.48–0.74) | 4.3 × 10−6 | 0.68 (0.46–1.02) | 0.062 | 0.57 (0.44–0.74) | 2 × 10−5 | |||||||
Impaired glucose tolerance 5 | GG | 934 (82.6) | 446 (82.8) | Ref. | 251 (82.0) | 165 (84.6) | Ref. | 683 (82.8) | 281 (81.7) | Ref. | |||
GA | 184 (16.3) | 89 (16.5) | 1.03 (0.77–1.38) | 0.825 | 50 (16.3) | 30 (15.4) | 0.84 (0.51–1.40) | 0.51 | 134 (16.2) | 59 (17.2) | 1.12 (0.79–1.59) | 0.52 | |
AA | 13 (1.2) | 4 (0.7) | 0.54 (0.17–1.70) | 0.292 | 5 (1.6) | - | 8 (1.0) | 4 (1.2) | 1.01 (0.30–3.47) | 0.983 | |||
Additive model | 0.96 (0.74–1.25) | 0.773 | 0.70 (0.44–1.12) | 0.135 | 1.10 (0.80–1.50) | 0.56 | |||||||
Type 2 Diabetes 6 | GG | 934 (82.6) | 220 (77.6) | Ref. | 251 (82.0) | 72 (82.8) | Ref. | 683 (82.8) | 148 (75.1) | Ref. | |||
GA | 184 (16.3) | 60 (21.1) | 1.56 (1.11–2.21) | 0.011 | 50 (16.3) | 14 (16.1) | 0.98 (0.49–1.97) | 0.954 | 134 (16.2) | 46 (23.4) | 1.82 (1.22–2.71) | 0.003 | |
AA | 13 (1.2) | 4 (1.4) | 0.97 (0.29–3.20) | 0.959 | 5 (1.6) | 1 (1.2) | 0.32 (0.03–3.61) | 0.355 | 8 (1.0) | 3 (1.5) | 1.39 (0.35–5.54) | 0.644 | |
Additive model | 1.39 (1.03–1.88) | 0.033 | 0.86 (0.46–1.59) | 0.634 | 1.62 (1.14–2.30) | 0.007 |
Total | Men | Women | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Outcome | Genotype | Control, n (%) | Case, n (%) | OR 1,7 (95% CI) | p Value | Control, n (%) | Case, n (%) | OR 2 (95% CI) | p Value | Control, n (%) | Case, n (%) | OR 2 (95% CI) | p Value |
MetS 3 | GG | 445 (49.0) | 534 (52.0) | Ref. | 161 (50.2) | 138 (51.3) | Ref. | 294 (48.4) | 396 (52.2) | Ref. | |||
GA | 391 (42.1) | 417 (40.6) | 0.84 (0.69–1.03) | 0.097 | 135 (42.1) | 117 (43.5) | 0.98 (0.67–1.34) | 0.780 | 256 (42.2) | 300 (39.5) | 0.80 (0.62–1.02) | 0.066 | |
AA | 82 (8.8) | 77 (7.5) | 0.65 (0.45–0.93) | 0.018 | 25 (7.8) | 14 (5.2) | 0.59 (0.29–1.19) | 0.138 | 63 (8.3) | 63 (8.3) | 0.67 (0.44–1.02) | 0.061 | |
Additive model | 0.82 (0.71–0.95) | 0.010 | 0.85 (0.65–1.12) | 0.258 | 0.81 (0.68–0.97) | 0.020 | |||||||
Low HDL-cholesterol 4 | GG | 308 (45.5) | 681 (53.2) | Ref. | 124 (48.4) | 175 (52.4) | Ref. | 184 (43.7) | 506 (53.5) | Ref. | |||
GA | 304 (44.9) | 504 (39.4) | 0.75 (0.61, 0.91) | 0.004 | 112 (43.8) | 140 (41.9) | 0.90 (0.64–1.27) | 0.546 | 192 (45.6) | 364 (38.5) | 0.67 (0.53–0.86) | 0.002 | |
AA | 65 (9.6) | 94 (7.4) | 0.63 (0.45, 0.90) | 0.011 | 20 (7.8) | 19 (5.7) | 0.66 (0.34–1.30) | 0.23 | 45 (10.7) | 75 (7.9) | 0.61 (0.40–0.93) | 0.020 | |
Additive model | 0.77 (0.67, 0.90) | 0.001 | 0.85 (0.65–1.12) | 0.249 | 0.74 (0.62–0.88) | 0.001 | |||||||
Impaired glucose tolerance 5 | GG | 567 (50.3) | 280 (51.7) | Ref. | 158 (52.0) | 102 (51.5) | Ref. | 409 (49.6) | 178 (51.7) | Ref. | |||
GA | 468 (41.5) | 222 (41.0) | 0.93 (0.75, 1.16) | 0.542 | 126 (41.5) | 87 (43.9) | 1.04 (0.71–1.52) | 0.831 | 342 (41.5) | 135 (39.2) | 0.89 (0.69–1.17) | 0.418 | |
AA | 93 (8.2) | 40 (7.4) | 0.83 (0.55, 1.26) | 0.388 | 20 (6.6) | 9 (4.6) | 0.65 (0.28–1.50) | 0.309 | 73 (8.9) | 31 (9.0) | 0.92 (0.57–1.47) | 0.729 | |
Additive model | 0.92 (0.78, 1.09) | 0.344 | 0.93 (0.69–1.26) | 0.625 | 0.93 (0.76–1.14) | 0.492 | |||||||
Type 2 Diabetes 6 | GG | 567 (50.3) | 142 (49.7) | Ref. | 158 (52.0) | 39 (44.3) | Ref. | 409 (49.6) | 103 (52.0) | Ref. | |||
GA | 468 (41.5) | 118 (41.3) | 0.96 (0.72, 1.29) | 0.800 | 126 (41.5) | 39 (44.3) | 1.25 (0.72–2.16) | 0.43 | 342 (41.5) | 79 (39.9) | 0.87 (0.62–1.23) | 0.432 | |
AA | 93 (8.2) | 26 (9.1) | 0.99 (0.60, 1.63) | 0.967 | 20 (6.6) | 10 (11.4) | 1.76 (0.70–4.41) | 0.23 | 73 (8.9) | 16 (8.1) | 0.78 (0.42–1.43) | 0.419 | |
Additive model | 0.98 (0.79, 1.22) | 0.87 | 1.31 (0.88–1.97) | 0.187 | 0.88 (0.68–1.13) | 0.314 |
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León-Reyes, G.; Rivera-Paredez, B.; López, J.C.F.; Ramírez-Salazar, E.G.; Aquino-Gálvez, A.; Gallegos-Carrillo, K.; Denova-Gutiérrez, E.; Salmerón, J.; Velázquez-Cruz, R. The Variant rs1784042 of the SIDT2 Gene is Associated with Metabolic Syndrome through Low HDL-c Levels in a Mexican Population. Genes 2020, 11, 1192. https://doi.org/10.3390/genes11101192
León-Reyes G, Rivera-Paredez B, López JCF, Ramírez-Salazar EG, Aquino-Gálvez A, Gallegos-Carrillo K, Denova-Gutiérrez E, Salmerón J, Velázquez-Cruz R. The Variant rs1784042 of the SIDT2 Gene is Associated with Metabolic Syndrome through Low HDL-c Levels in a Mexican Population. Genes. 2020; 11(10):1192. https://doi.org/10.3390/genes11101192
Chicago/Turabian StyleLeón-Reyes, Guadalupe, Berenice Rivera-Paredez, Juan Carlos Fernandez López, Eric G. Ramírez-Salazar, Arnoldo Aquino-Gálvez, Katia Gallegos-Carrillo, Edgar Denova-Gutiérrez, Jorge Salmerón, and Rafael Velázquez-Cruz. 2020. "The Variant rs1784042 of the SIDT2 Gene is Associated with Metabolic Syndrome through Low HDL-c Levels in a Mexican Population" Genes 11, no. 10: 1192. https://doi.org/10.3390/genes11101192
APA StyleLeón-Reyes, G., Rivera-Paredez, B., López, J. C. F., Ramírez-Salazar, E. G., Aquino-Gálvez, A., Gallegos-Carrillo, K., Denova-Gutiérrez, E., Salmerón, J., & Velázquez-Cruz, R. (2020). The Variant rs1784042 of the SIDT2 Gene is Associated with Metabolic Syndrome through Low HDL-c Levels in a Mexican Population. Genes, 11(10), 1192. https://doi.org/10.3390/genes11101192