Exploring the Relationship of rs2802292 with Diabetes and NAFLD in a Southern Italian Cohort—Nutrihep Study
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Lifestyle, Clinical, and Dietary Assessment
4.3. DNA Extraction and TaqMan PCR Assay
4.4. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameters * | Total Cohort (n = 650) | Genotypes | p ^ | Multiple Comparisons Ψ | ||||
---|---|---|---|---|---|---|---|---|
Homozygous Minor (GG) (n = 163) (a) | Heterozygous (GT) (n = 334) (b) | Homozygous Major (TT) (n = 153) (c) | (b) vs. (a) | (c) vs. (a) | (c) vs. (b) | |||
Gender (M) (%) | 274 (42.15) | 65 (39.88) | 142 (42.51) | 67 (43.79) | 0.77 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
Age (yrs) | 61.25 ± 11.91 | 61.93 ± 12.50 | 60.70 ± 11.73 | 61.72 ± 11.68 | 0.30 | 0.46 | 0.99 | 0.23 |
Age Classes (%) (yrs) | 0.37 † | 0.99 ¥ | 0.99 ¥ | 0.50 ¥ | ||||
Adults (≤65) | 394 (60.62) | 98 (60.12) | 210 (62.87) | 86 (56.21) | ||||
Elderly (>65) | 256 (39.38) | 65 (39.88) | 124 (37.13) | 67 (43.79) | ||||
Education (%) | 0.08 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ | ||||
None | 14 (2.26) | 4 (2.60) | 4 (1.25) | 6 (4.08) | ||||
Elementary School | 193 (31.13) | 44 (28.57) | 99 (31.03) | 50 (34.01) | ||||
Secondary School | 204 (32.90) | 51 (33.12) | 101 (31.66) | 52 (35.37) | ||||
High School | 163 (26.29) | 43 (27.92) | 90 (28.21) | 30 (20.41) | ||||
Degree | 22 (3.55) | 7 (4.55) | 15 (4.70) | 0 (0.00) | ||||
Post-Degree | 24 (3.87) | 5 (3.25) | 10 (3.13) | 9 (6.12) | ||||
Civil Status (%) | 0.68 † | 0.99 ¥ | 0.89 ¥ | 0.57 ¥ | ||||
Single | 48 (7.74) | 14 (9.09) | 26 (8.15) | 8 (5.44) | ||||
Married or Cohabiting | 508 (81.94) | 126 (81.82) | 257 (80.56) | 125 (85.03) | ||||
Divorced or Separated | 17 (2.74) | 3 (1.95) | 12 (3.76) | 2 (1.36) | ||||
Widow/er | 47 (7.58) | 11 (7.14) | 24 (7.52) | 12 (8.16) | ||||
Smoker (Yes) (%) | 71 (11.40) | 18 (11.46) | 37 (11.56) | 16 (10.96) | 0.98 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
Waist Circumference (cm) | 93.68 ± 12.64 | 92.90 ± 11.91 | 93.49 ± 12.54 | 94.94 ± 13.56 | 0.31 | 0.99 | 0.28 | 0.24 |
Hip Circumference (cm) | 103.58 ± 9.32 | 103.56 ± 9.52 | 103.44 ± 9.17 | 103.92 ± 9.48 | 0.89 | 0.99 | 0.98 | 0.99 |
BMI (Kg/m2) | 28.24 ± 4.70 | 28.27 ± 4.51 | 28.16 ± 4.51 | 28.39 ± 5.31 | 0.96 | 0.99 | 0.99 | 0.99 |
Systolic Blood Pressure (mmHg) | 124.91 ± 15.15 | 124.81 ± 14.72 | 124.85 ± 15.07 | 125.16 ± 15.87 | 0.95 | 0.99 | 0.99 | 0.99 |
Diastolic Blood Pressure (mmHg) | 78.65 ± 7.70 | 78.49 ± 7.33 | 78.94 ± 7.92 | 78.20 ± 7.60 | 0.55 | 0.68 | 0.99 | 0.48 |
Diabetes (Yes) (%) | 58 (8.92) | 13 (7.98) | 23 (6.89) | 22 (14.38) | 0.02 † | 0.99 ¥ | 0.21 ¥ | 0.05 ¥ |
Hypertension (Yes) (%) | 261 (42.16) | 63 (40.38) | 134 (42.14) | 64 (44.14) | 0.80 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
Ulcer (Yes) (%) | 38 (6.14) | 9 (5.77) | 18 (5.66) | 11 (7.59) | 0.71 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
Heart Attack (Yes) (%) | 15 (2.42) | 2 (1.28) | 7 (2.20) | 6 (4.14) | 0.29 † | 0.99 ¥ | 0.39 ¥ | 0.88 ¥ |
Stroke (Yes) (%) | 2 (0.32) | 1 (0.64) | 1 (0.31) | 0 (0.00) | 0.74 † | 0.99 ¥ | -- | -- |
NAFLD (Yes) (%) | 393 (60.46) | 98 (60.12) | 199 (59.58) | 96 (62.75) | 0.80 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
HOMA | 1.98 ± 1.91 | 1.90 ± 1.08 | 2.00 ± 2.38 | 2.03 ± 1.38 | 0.20 | 0.29 | 0.99 | 0.18 |
Out of Range (>2.5) (%) | 142 (22.12) | 35 (22.01) | 64 (19.34) | 43 (28.29) | 0.09 † | 0.99 ¥ | 0.61 ¥ | 0.11 ¥ |
Glycemia (mg/dL) | 99.14 ± 17.61 | 98.84 ± 18.15 | 98.40 ± 17.44 | 101.07 ± 17.38 | 0.13 | 0.99 | 0.13 | 0.10 |
Out of Range (60–110) (%) | 91 (14.02) | 20 (12.35) | 41 (12.28) | 30 (19.61) | 0.07 † | 0.99 ¥ | 0.24 ¥ | 0.14 ¥ |
Insulin (mmol/L) | 7.77 ± 4.98 | 7.50 ± 3.30 | 7.77 ± 5.56 | 8.03 ± 5.13 | 0.21 | 0.16 | 0.99 | 0.35 |
Out of Range (1.9–23) (%) | 13 (2.02) | 3 (1.89) | 6 (1.81) | 4 (2.63) | 0.82 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
Cholesterol (mg/dL) | 194.96 ± 36.37 | 197.93 ± 38.22 | 196.86 ± 34.40 | 187.69 ± 37.79 | 0.03 | 0.96 | 0.02 | 0.03 |
Out of Range (>220) (%) | 156 (24.04) | 45 (27.78) | 81 (24.25) | 30 (19.61) | 0.23 † | 0.99 ¥ | 0.26 ¥ | 0.73 ¥ |
Triglycerides (mg/dL) | 105.71 ± 67.45 | 115.42 ± 72.65 | 103.04 ± 63.38 | 101.23 ± 69.76 | 0.11 | 0.11 | 0.09 | 0.99 |
Out of Range (36–165) (%) | 111 (17.10) | 34 (20.99) | 53 (15.87) | 24 (15.69) | 0.32 † | 0.53 ¥ | 0.67 ¥ | 0.99 ¥ |
HDL (mg %) | 50.86 ± 12.63 | 50.65 ± 13.02 | 50.82 ± 12.49 | 51.16 ± 12.60 | 0.81 | 0.99 | 0.77 | 0.98 |
Out of Range (40–60) (%) | 253 (38.98) | 60 (37.04) | 131 (39.22) | 62 (40.52) | 0.81 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
RBC (106/µL) | 4.96 ± 0.52 | 4.92 ± 0.54 | 4.98 ± 0.52 | 4.96 ± 0.51 | 0.41 | 0.30 | 0.45 | 0.99 |
Out of Range (3.83–5.08) (%) | 244 (37.60) | 57 (35.19) | 129 (38.62) | 58 (37.91) | 0.76 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
Hemoblogin (g/dL) | 14.04 ± 1.45 | 13.96 ± 1.49 | 14.12 ± 1.40 | 13.95 ± 1.52 | 0.44 | 0.43 | 0.99 | 0.46 |
Out of Range (11.7–15.5) (%) | 122 (18.80) | 33 (20.37) | 62 (18.56) | 27 (17.65) | 0.82 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
Hematocrit (L/L) | 42.30 ± 3.72 | 42.11 ± 3.83 | 42.46 ± 3.55 | 42.16 ± 3.95 | 0.55 | 0.49 | 0.99 | 0.66 |
Out of Range (34.5–46.3) (%) | 94 (14.48) | 25 (15.43) | 47 (14.07) | 22 (14.38) | 0.92 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
MCV (fL) | 85.77 ± 7.43 | 86.09 ± 7.24 | 85.77 ± 7.04 | 85.44 ± 8.43 | 0.62 | 0.52 | 0.99 | 0.89 |
Out of Range (80.4–95.9) (%) | 80 (12.33) | 20 (12.35) | 36 (10.78) | 24 (15.69) | 0.31 † | 0.99 ¥ | 0.99 ¥ | 0.45 ¥ |
MCH (pg) | 28.46 ± 2.77 | 28.54 ± 2.77 | 28.51 ± 2.62 | 28.25 ± 3.06 | 0.65 | 0.97 | 0.53 | 0.80 |
Out of Range (27.2–33.5) (%) | 112 (17.26) | 32 (19.75) | 51 (15.27) | 29 (18.95) | 0.38 † | 0.68 ¥ | 0.99 ¥ | 0.97 ¥ |
MCHC (g/dL) | 33.16 ± 1.08 | 33.12 ± 1.10 | 33.23 ± 1.08 | 33.04 ± 1.03 | 0.11 | 0.39 | 0.65 | 0.07 |
Out of Range (32.5–35.2) (%) | 176 (27.12) | 45 (27.78) | 86 (25.75) | 45 (29.41) | 0.68 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
RDW-CV (%) | 13.87 ± 1.48 | 13.93 ± 1.66 | 13.80 ± 1.39 | 13.95 ± 1.51 | 0.25 | 0.43 | 0.99 | 0.18 |
Out of Range (10–15) (%) | 76 (11.71) | 19 (11.73) | 37 (11.08) | 20 (13.07) | 0.82 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
Platelets (103/µL) | 230.88 ± 56.01 | 236.08 ± 65.02 | 229.02 ± 52.32 | 229.41 ± 53.50 | 0.58 | 0.44 | 0.78 | 0.99 |
Out of Range (159–388) (%) | 52 (8.01) | 12 (7.41) | 24 (7.19) | 16 (10.46) | 0.44 † | 0.99 ¥ | 0.99 ¥ | 0.75 ¥ |
WBC (103/µL) | 5.89 ± 1.86 | 5.73 ± 1.56 | 5.97 ± 2.11 | 5.87 ± 1.56 | 0.60 | 0.69 | 0.49 | 0.99 |
Out of Range (4.1–11.2) (%) | 75 (11.56) | 21 (12.96) | 42 (12.57) | 12 (7.84) | 0.26 † | 0.99 ¥ | 0.40 ¥ | 0.28 ¥ |
Neutrophils (%) | 57.77 ± 7.74 | 58.28 ± 7.43 | 57.40 ± 7.93 | 58.03 ± 7.65 | 0.50 | 0.39 | 0.99 † | 0.75 † |
Out of Range (39.9–73) (%) | 27 (4.16) | 7 (4.32) | 14 (4.19) | 6 (3.92) | 0.98 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
Lymphocytes (%) | 31.47 ± 7.26 | 30.95 ± 7.25 | 31.86 ± 7.37 | 31.19 ± 7.02 | 0.55 | 0.49 | 0.99 | 0.64 |
Out of Range (18.8–50.8) (%) | 35 (5.39) | 11 (6.79) | 15 (4.49) | 9 (5.88) | 0.54 † | 0.94 ¥ | 0.99 ¥ | 0.99 ¥ |
Monocytes (%) | 7.36 ± 1.67 | 7.48 ± 1.73 | 7.33 ± 1.52 | 7.30 ± 1.91 | 0.30 | 0.60 | 0.18 | 0.50 |
Out of Range (4.1–12.2) (%) | 13 (2.00) | 4 (2.47) | 2 (0.60) | 7 (4.58) | 0.009 † | 0.44 ¥ | 0.94 ¥ | 0.07 ¥ |
Basophils (%) | 0.54 ± 0.33 | 0.53 ± 0.31 | 0.55 ± 0.35 | 0.51 ± 0.30 | 0.20 | 0.48 | 0.77 | 0.13 |
Out of Range (0.3–1.8) (%) | 89 (13.71) | 24 (14.81) | 40 (11.98) | 25 (16.34) | 0.38 † | 0.99 ¥ | 0.99 ¥ | 0.63 ¥ |
Neutrophils (109/L) | 3.45 ± 1.43 | 3.38 ± 1.16 | 3.49 ± 1.65 | 3.43 ± 1.17 | 0.73 | 0.99 | 0.72 | 0.73 |
Out of Range (1.8–6.4) (%) | 40 (6.16) | 8 (4.94) | 25 (7.49) | 7 (4.58) | 0.35 † | 0.76 ¥ | 0.99 ¥ | 0.57 ¥ |
Lymphocytes (103/µL) | 1.81 ± 0.58 | 1.73 ± 0.50 | 1.85 ± 0.60 | 1.81 ± 0.60 | 0.23 | 0.13 | 0.58 | 0.75 |
Out of Range (1.2–3.6) (%) | 61 (9.40) | 19 (11.73) | 27 (8.08) | 15 (9.80) | 0.42 † | 0.64 ¥ | 0.99 ¥ | 0.99 ¥ |
Monocytes (103/µL) | 0.43 ± 0.15 | 0.43 ± 0.17 | 0.43 ± 0.15 | 0.42 ± 0.13 | 0.86 | 0.98 | 0.99 | 0.99 |
Out of Range (0.3–0.9) (%) | 117 (18.03) | 35 (21.60) | 56 (16.77) | 26 (16.99) | 0.39 † | 0.62 ¥ | 0.90 ¥ | 0.99 ¥ |
Basophils (103/µL) | 0.03 ± 0.05 | 0.03 ± 0.02 | 0.03 ± 0.07 | 0.03 ± 0.02 | 0.42 | 0.37 | 0.99 | 0.51 |
Out of Range (0–0.2) (%) | 1 (0.15) | 0 (0.00) | 1 (0.30) | 0 (0.00) | 0.99 † | -- | -- | -- |
Eosinophils (103/µL) | 0.17 ± 0.15 | 0.16 ± 0.16 | 0.17 ± 0.13 | 0.17 ± 0.17 | 0.37 | 0.26 | 0.40 | 0.99 |
Out of Range (0.1–0.5) (%) | 202 (31.12) | 57 (35.19) | 103 (30.84) | 42 (27.45) | 0.33 † | 0.99 ¥ | 0.41 ¥ | 0.99 ¥ |
HbA1c (mmol/mol) | 38.08 ± 7.68 | 38.67 ± 8.67 | 37.57 ± 6.84 | 38.55 ± 8.24 | 0.45 | 0.61 | 0.99 | 0.36 |
Out of Range (20–42) (%) | 113 (17.44) | 26 (16.05) | 52 (15.62) | 35 (22.88) | 0.13 † | 0.99 ¥ | 0.38 ¥ | 0.20 ¥ |
Total Bilirubin (mg/dL) | 0.70 ± 0.36 | 0.67 ± 0.30 | 0.70 ± 0.36 | 0.75 ± 0.41 | 0.44 | 0.83 | 0.31 | 0.57 |
Out of Range (0.1–1.2) (%) | 65 (10.02) | 11 (6.79) | 32 (9.58) | 22 (14.38) | 0.07 † | 0.82 ¥ | 0.09 ¥ | 0.42 ¥ |
Direct Bilirubin (mg/dL) | 0.17 ± 0.05 | 0.17 ± 0.05 | 0.17 ± 0.05 | 0.18 ± 0.06 | 0.51 | 0.99 | 0.43 | 0.49 |
Out of Range (0.1–0.5) (%) | 4 (0.62) | 1 (0.63) | 2 (0.60) | 1 (0.65) | 0.99 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
GOT (U/L) | 22.30 ± 8.67 | 23.51 ± 14.08 | 22.23 ± 6.19 | 21.17 ± 4.87 | 0.18 | 0.87 | 0.11 | 0.20 |
Out of Range (0–30) (%) | 38 (5.86) | 10 (6.17) | 22 (6.59) | 6 (3.92) | 0.50 † | 0.99 ¥ | 0.99 ¥ | 0.60 ¥ |
SGPT (U/L) | 22.22 ± 12.05 | 22.28 ± 15.04 | 22.88 ± 11.89 | 20.71 ± 8.14 | 0.17 † | 0.38 | 0.84 | 0.11 |
Out of Range (0–30) (%) | 77 (11.86) | 18 (11.11) | 49 (14.67) | 10 (6.54) | 0.03 † | 0.77 ¥ | 0.45 ¥ | 0.01 ¥ |
GGT (U/L) | 17.82 ± 13.84 | 18.72 ± 17.98 | 17.68 ± 12.77 | 17.17 ± 10.75 | 0.61 | 0.99 | 0.61 | 0.52 |
Out of Range (7–22) (%) | 111 (17.10) | 26 (16.05) | 60 (17.96) | 25 (16.34) | 0.93 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
Alkaline Phosphatase (U/L) | 56.44 ± 16.42 | 57.31 ± 15.69 | 56.03 ± 16.58 | 56.42 ± 16.88 | 0.34 | 0.21 | 0.54 | 0.99 |
Out of Range (38–126) (%) | 52 (8.04) | 13 (8.02) | 31 (9.28) | 8 (5.30) | 0.33 † | 0.99 ¥ | 0.99 ¥ | 0.30 ¥ |
Albumin (g/dL) | 4.07 ± 0.27 | 4.08 ± 0.31 | 4.08 ± 0.26 | 4.05 ± 0.24 | 0.72 | 0.99 | 0.99 | 0.64 |
Out of Range (3.5–5.5) (%) | 7 (1.13) | 4 (2.58) | 1 (0.31) | 2 (1.36) | 0.06 † | 0.25 ¥ | 0.99 ¥ | 0.89 ¥ |
Iron (µg/dL) | 90.35 ± 31.20 | 90.69 ± 32.25 | 89.46 ± 30.29 | 91.95 ± 32.15 | 0.59 | 0.99 | 0.70 | 0.47 |
Out of Range (49–151) (%) | 71 (10.97) | 21 (13.04) | 34 (10.18) | 16 (10.53) | 0.62 † | 0.99 ¥ | 0.99 ¥ | 0.99 ¥ |
Ferritin (ng/mL) | 91.48 ± 83.35 | 88.09 ± 85.05 | 95.84 ± 88.09 | 85.55 ± 69.75 | 0.34 | 0.26 | 0.99 | 0.48 |
Out of Range (11–200) (%) | 542 (83.51) | 134 (82.72) | 284 (85.03) | 124 (81.05) | 0.52 † | 0.99 ¥ | 0.99 ¥ | 0.85 ¥ |
Ceruloplasmin (mg/dL) | 30.83 ± 6.49 | 31.83 ± 6.24 | 30.49 ± 6.43 | 30.49 ± 6.80 | 0.04 | 0.02 | 0.06 | 0.99 |
Out of Range (25–63) (%) | 112 (17.26) | 16 (9.88) | 68 (20.36) | 28 (18.30) | 0.01 † | 0.004 ¥ | 0.09 ¥ | 0.99 ¥ |
α1AT (mg/dL) | 172.25 ± 27.36 | 175.10 ± 28.26 | 171.00 ± 27.82 | 171.95 ± 25.26 | 0.08 | 0.04 | 0.17 | 0.99 |
Out of Range (90–200) (%) | 86 (13.25) | 30 (18.52) | 40 (11.98) | 16 (10.46) | 0.07 † | 0.19 ¥ | 0.12 ¥ | 0.99 ¥ |
Genotypes | OR | se (OR) | 95% C.I. | p |
---|---|---|---|---|
GG [Ref.] | -- | -- | -- | -- |
GT | 0.95 | 0.35 | 0.46 to 1.98 | 0.90 |
TT | 2.14 | 0.82 | 1.01 to 4.53 | 0.05 |
G-Carriers | ||||
TT [Ref.] | -- | -- | -- | -- |
GG/GT | 0.45 | 0.13 | 0.25 to 0.81 | 0.008 |
Effects | β | se (β) | 95% C.I. | p |
---|---|---|---|---|
Indirect | ||||
rs2802292 (GT) → Diabetes → NAFLD | −0.001 | 0.006 | −0.01 to 0.01 | 0.84 |
rs2802292 (TT) → Diabetes → NAFLD | 0.01 | 0.008 | −0.001 to 0.03 | 0.08 |
Component | ||||
rs2802292 (GT) → Diabetes | −0.01 | 0.03 | −0.06 to 0.05 | 0.83 |
rs2802292 (TT) → Diabetes | 0.10 | 0.03 | 0.003 to 0.12 | 0.04 |
Diabetes → NAFLD | 0.13 | 0.06 | 0.10 to 0.35 | <0.001 |
Direct | ||||
rs2802292 (GT) → NAFLD | 0.008 | 0.04 | −0.08 to 0.09 | 0.85 |
rs2802292 (TT) → NAFLD | 0.009 | 0.05 | −0.09 to 0.11 | 0.84 |
Total | ||||
rs2802292 (GT) → NAFLD | 0.007 | 0.04 | −0.08 to 0.09 | 0.88 |
rs2802292 (TT) → NAFLD | 0.02 | 0.05 | −0.08 to 0.13 | 0.63 |
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Forte, G.; Donghia, R.; Lepore Signorile, M.; Tatoli, R.; Bonfiglio, C.; Losito, F.; De Marco, K.; Manghisi, A.; Guglielmi, F.A.; Disciglio, V.; et al. Exploring the Relationship of rs2802292 with Diabetes and NAFLD in a Southern Italian Cohort—Nutrihep Study. Int. J. Mol. Sci. 2024, 25, 9512. https://doi.org/10.3390/ijms25179512
Forte G, Donghia R, Lepore Signorile M, Tatoli R, Bonfiglio C, Losito F, De Marco K, Manghisi A, Guglielmi FA, Disciglio V, et al. Exploring the Relationship of rs2802292 with Diabetes and NAFLD in a Southern Italian Cohort—Nutrihep Study. International Journal of Molecular Sciences. 2024; 25(17):9512. https://doi.org/10.3390/ijms25179512
Chicago/Turabian StyleForte, Giovanna, Rossella Donghia, Martina Lepore Signorile, Rossella Tatoli, Caterina Bonfiglio, Francesco Losito, Katia De Marco, Andrea Manghisi, Filomena Anna Guglielmi, Vittoria Disciglio, and et al. 2024. "Exploring the Relationship of rs2802292 with Diabetes and NAFLD in a Southern Italian Cohort—Nutrihep Study" International Journal of Molecular Sciences 25, no. 17: 9512. https://doi.org/10.3390/ijms25179512