TABLE 2.
Proportions of C282Y homozygotes and control participants with symptoms and signs
| Symptoms and clinical conditions |
C282Y homozygotes |
Control participants (n=364) | Nominal P ‡ | ||
|---|---|---|---|---|---|
| Previously diagnosed (n=87) |
Newly diagnosed |
||||
| Ferritin elevated*(n=131) | Ferritin not elevated† (n=64) | ||||
| General manifestations | |||||
| Chronic fatigue/weakness in the last 12 months§ | 51.7 | 39.7 | 34.4 | 23.6 | <0.001 |
| Unexplained weight loss in the last 12 months § | 5.8 | 6.9 | 3.1 | 0.0 | <0.001 |
| Health Survey score (mean)§ | 60.3 | 70.1 | 66.8 | 69.5 | 0.066 |
| Cardiac symptoms | |||||
| Swelling of feet or ankles in the last 12 months§ | 41.4 | 37.4 | 32.8 | 34.1 | 0.70 |
| Shortness of breath when walking quickly or uphill | 69.0 | 62.6 | 65.6 | 61.3 | 0.62 |
| Shortness of breath when walking on level ground | 27.6 | 12.2 | 20.3 | 12.1 | 0.033 |
| Shortness of breath while resting in a chair | 6.9 | 3.8 | 6.3 | 2.5 | 0.61 |
| Shortness of breath in the last 12 months | 41.4 | 29.8 | 31.3 | 23.6 | 0.10 |
| Heart failure or weak heart, ever | 9.2 | 1.5 | 3.1 | 5.2 | 0.33 |
| Abnormal heart rhythm, heart beat or action arrhythmia, ever | 23.0 | 15.3 | 18.8 | 21.2 | 0.74 |
| Other heart disease or heart attack, ever | 10.3 | 8.4 | 7.8 | 11.0 | 0.41 |
| Diabetes | |||||
| Diabetes, ever | 16.1 | 9.9 | 10.9 | 8.5 | 0.57 |
| Liver disease | |||||
| Abdominal swelling or fluid in last 12 months§ | 16.1 | 11.5 | 20.3 | 8.8 | 0.42 |
| Unexplained abdominal pain or discomfort in the last 12 months§ | 23.0 | 16.8 | 28.1 | 11.3 | 0.037 |
| Liver disease, ever§ | 16.1 | 9.2 | 7.8 | 6.0 | 0.094 |
| Porphyria cutanea tarda, ever§ | 4.6 | 0.8 | 1.6 | 0.3 | 0.038 |
| Arthritis | |||||
| Joint stiffness/pain/ache in last 12 months§ | 73.6 | 74.1 | 70.3 | 55.5 | <0.001 |
| Arthritis, ever§ | 57.5 | 35.1 | 29.7 | 38.7 | 0.084 |
| Neurological symptoms | |||||
| Unexplained confusion or memory loss in last 12 months | 27.6 | 16.8 | 18.8 | 9.1 | 0.078 |
| Hypogonadism | |||||
| Trouble having an erection or loss of sexual drive in last 12 months (men only) | 56.3¶ | 44.4** | 44.4†† | 36.6‡‡ | 0.023 |
| Other endocrine | |||||
| Thyroid disease, ever | 16.1 | 15.3 | 21.9 | 19.8 | 0.93 |
| Skin changes | |||||
| Change in skin colour in last 12 months§ | 12.6 | 10.7 | 12.5 | 3.0 | 0.0015 |
| Bone disease | |||||
| Osteoporosis, ever | 8.1 | 3.8 | 7.8 | 7.1 | 0.51 |
| Other | |||||
| Cancer§ | 10.3 | 16.8 | 14.1 | 14.3 | 0.048 |
| Signs on physical examination | |||||
| Heart arrhythmia: bradycardia | 0.0 | 0.0 | 0.0 | 0.0§§ | 1.00 |
| Heart arrhythmia: tachycardia | 1.2 | 0.0 | 0.0 | 0.0§§ | 0.23 |
| Frequent premature contractions (>1 ectopic beat/min) | 6.9 | 3.1 | 3.1 | 1.7§§ | 0.049 |
| Other abnormal rhythm | 3.5 | 0.0 | 0.0 | 3.3§§ | 0.058 |
| Heart murmur | 8.1 | 6.1 | 7.8 | 10.2§§ | 0.51 |
| Edema§ | 11.5 | 7.6 | 6.3 | 15.5§§ | 0.73 |
| Hepatomegaly§ | 10.3 | 9.2 | 4.7 | 3.3§§ | 0.068 |
| Splenomegaly§ | 2.3 | 0.0 | 1.6 | 0.6§§ | 0.14 |
| Metacarpophalangeal joints swollen or tender§ | 21.8 | 13.7 | 3.1 | 5.0§§ | <0.001 |
| Increased pigmentation on sun-exposed or unexposed areas§ | 21.8 | 9.9 | 7.8 | 4.4§§ | <0.001 |
| Blistering, ulcers, scarring of sun-exposed skin§ | 3.5 | 2.3 | 0.0 | 2.5§§ | 0.64 |
| Hypertrichosis (excess hair growth in sun-exposed areas)§ | 0.0 | 1.5 | 1.6 | 0.3§§ | 0.17 |
*
Serum ferritin > 200 μg/L for women, >300 μg/L for men.
†
Serum ferritin ≤ 200 μg/L for women, ≤ 300 μg/L for men.
‡
P value for the group effect from logistic regression or Fisher’s exact test. Nominal P values are compared with 0.00139 (0.05/36) to assess significance with a 5% type-1 error rate;
§
Outcomes possibly subject to bias in comparisons between C282Y homozygotes and controls;
¶
Denominator = 48;
**
Denominator = 63;
††
Denominator = 9;
‡‡
Denominator = 142;
§§
Denominator = 362