HFE Genetic Variability, Body Iron Stores, and the Risk of Type 2 Diabetes in U.S. Women
Article Figures & Tables
Figures
- FIG. 1.
Meta-analysis of HFE variants C282Y (17 studies) (A), H63D (13 studies) (B), and the compound heterozygotes (6 studies, Kankova’s study had two populations) (C) and type 2 diabetes. All included studies are listed in the references (14–29). Boxes indicate the OR in each study, with the size of the square inversely proportional to its variance; horizontal lines represent the 95% CI; unshaded diamonds indicate the pooled OR and its 95% CI.
- FIG. 2.
The modification effects of carrying either H63D or C282Y on the associations between intake of heme iron (in quartiles) and the risk of type 2 diabetes. The corresponding 95% CIs are presented in parenthesis. ▪, ORs among subjects with either variant H63D or C282Y; ♦, ORs among subjects with the wild-type genotypes.
Tables
- TABLE 1
Age-standardized diabetes risk factors in case and control subjects in U.S. women
Case subjects Control subjects P n 714 1120 Age (years) 54.4 54.5 0.83 BMI (kg/m2) 30.4 27.2 <0.001 Physical activity (metabolic equivalent task hours/week) 12.2 14.9 <0.001 Alcohol consumption (g/day) 2.9 5.2 <0.001 Ethnicity (% white) 95.1 95.6 0.60 Current smoker (%) 14.5 12.0 0.11 Postmenopausal status (%) 75.6 75.3 0.52 Family history of diabetes (%) 46.8 22.3 <0.001 Biomarkers Insulin (μU/ml)* 13.8 10.5 <0.001 Proinsulin (fmol/ml) 26.0 11.7 <0.001 CRP (mg/dl) 0.52 0.23 <0.001 Ferritin (ng/ml) 69.4 46.5 <0.001 Ratio of transferrin receptor to ferritin 46.1 64.1 <0.001 Dietary intakes Total iron (mg/day) 17.3 17.4 0.90 Nonsupplemental iron (mg/day) 12.3 12.5 0.39 Supplemental iron (mg/day) 4.9 4.9 0.90 Heme iron (mg/day) 1.12 1.06 0.001 Red meat (servings/day × 1,000 kcal) 1.21 1.12 0.002 - *
* Insulin and proinsulin were measured in fasting samples only (insulin in 415 case subjects and 570 control subjects and proinsulin in 200 case subjects and 306 control subjects).
- *
- TABLE 2
Body iron stores by HFE variants H63D, C282Y, and the compound heterozygotes*
H63D P C282Y P The compound heterozygotes P HH HD DD DD vs. HH DD vs. HD CC CY + YY HHCC HDCY Ferritin (ng/ml) Control 782 (44.7) 302 (48.4) 24 (82.3) 0.03 0.06 982 (45.2) 137 (58.0) 0.03 669 (43.4) 23 (73.7) 0.03 Diabetic 498 (69.4) 184 (68.0) 23 (86.5) 0.32 0.28 616 (67.4) 94 (87.4) 0.03 423 (67.4) 21 (121.5) 0.01 Total 1,280 (55.1) 486 (57.4) 47 (85.6) 0.01 0.02 1,598 (54.6) 231 (72.2) 0.0006 1,092 (53.5) 44 (99.5) 0.0002 Ratio of transferrin receptor to ferritin Control 782 (66.7) 302 (60.9) 24 (32.1) 0.02 0.03 982 (66.7) 137 (47.9) 0.006 669 (70.1) 23 (38.5) 0.02 Diabetic 498 (46.5) 184 (45.2) 23 (30.9) 0.07 0.11 616 (47.5) 94 (34.5) 0.01 423 (48.9) 21 (22.4) 0.002 Total 1,280 (56.3) 486 (52.5) 47 (31.2) 0.001 0.005 1,598 (56.8) 231 (40.0) <0.0001 1,092 (59.1) 44 (27.7) <0.0001 Data are n (means).
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* Adjusting for age, BMI, alcohol consumption, smoking, physical activity, aspirin use, family history of diabetes, and postmenopausal hormone use.
- TABLE 3
Associations of HFE variants H63D, C282Y, and the compound heterozygotes with the risk of type 2 diabetes among U.S. women
Variants Control subjects Case subjects OR Age and BMI adjusted Multivariate adjusted* H63D HH 782 (70.6) 489 (70.6) 1.0 1.0 HD 302 (27.3) 184 (26.1) 0.97 (0.78–1.22) 0.95 (0.75–1.20) DD 24 (2.1) 23 (3.3) 1.68 (0.91–3.12) 1.84 (0.96–3.53) C282Y CC 982 (87.8) 616 (86.8) 1.0 1.0 CY + YY 137 (12.2) 94 (13.2) 1.13 (0.84–1.52) 1.16 (0.85–1.59) Compound heterozygotes HHCC 669 (96.7) 423 (95.3) 1.0 1.0 HDCY 23 (3.3) 21 (4.7) 1.61 (0.86–3.02) 1.57 (0.80–3.09) Data are n (%) or OR (95% CI).
- *
* Adjusting for age, BMI, alcohol consumption, smoking, physical activity, family history of diabetes, race, and postmenopausal hormone use.
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