Table 1. Description of cases and controls and their genotypes at MTHFR polymorphism rs1801133.
| Study (ref.) | Ethnicity | Cases/Controls | Serious DM-related complicationsa | Duration of DM (yr)b | Genotype by PCR-RFLP | PHWE c | |||||||
| Cases | Controls | ||||||||||||
| CC | CT | TT | CC | CT | TT | ||||||||
| Asian | |||||||||||||
| Bazzaz 2010 [46] | Iranian | 281/207 | NR | NR | 148 | 102 | 31 | 113 | 80 | 14 | 1.000 | ||
| Chang 2011 [27] | Taiwanese | 56/62 | NR | NR | 1 | 25 | 30 | 3 | 23 | 36 | 1.000 | ||
| Chauhan 2012 [43] | Indian | 1018/1006 | NR | NR | 31 | 310 | 677 | 45 | 335 | 626 | 1.000 | ||
| Chen 2010 [29] | Chinese | 40/55 | No metabolic syndrome, inflammatory disease, kidney disease, or coronary heart disease | NR | 23 | 13 | 4 | 34 | 17 | 4 | 0.439 | ||
| Dai 2012 [26] | Chinese | 60/60 | No diabetic nephropathy | 11.7±0.9 | 29 | 28 | 3 | 31 | 27 | 2 | 0.310 | ||
| Eroglu 2007 [47] | Turkish | 56/128 | No diabetic nephropathy | NR | 25 | 25 | 6 | 63 | 58 | 7 | 0.272 | ||
| Hasegawa 2003 [45] | Japanese | 62/200 | No renal failure or macroangiopathy. Retinopathy present in 77.4% of cases. | 18.5 (10–40) | 23 | 32 | 7 | 78 | 96 | 26 | 0.762 | ||
| Ho 2005 [36] | Taiwanese | 20/42 | Normal renal function; no deep vein thrombosis or coronary artery disease | NR | 13 | 5 | 2 | 28 | 11 | 3 | 0.326 | ||
| Luo 2009 [31] | Chinese | 71/85 | No cardiovascular disease or coronary heart disease | NR | 39 | 26 | 6 | 43 | 31 | 11 | 0.204 | ||
| Mao 2004 [37] | Chinese | 41/47 | No cerebrovascular disease | 5.68±4.22 | 19 | 17 | 5 | 26 | 18 | 3 | 1.000 | ||
| Mei 2012 [28] | Chinese | 116/124 | NR | NR | 19 | 70 | 27 | 14 | 73 | 37 | 0.025 | ||
| Movva 2011 [44] | Indian | 100/100 | No history or family history of renal complications | 12.16±4.07 | 68 | 32 | 0 | 91 | 9 | 0 | 1.000 | ||
| Raza 2012 [21] | Indian | 87/88 | NR | NR | 35 | 37 | 15 | 49 | 26 | 13 | 0.009 | ||
| Shi 2006 [33] | Chinese | 104/110 | No microvascular complications | NR | 70 | 29 | 5 | 68 | 34 | 8 | 0.273 | ||
| Sun 2006 [7] | Chinese | 104/114 | No overt nephropathy, cerebrovascular disease, coronary heart disease or peripheral vascular disease | 7.04±4.71 | 60 | 27 | 17 | 63 | 31 | 20 | <0.001 | ||
| Tutuncu 2005 [48] | Turkish | 87/91 | Coronary artery disease present in 18% of cases; cerebrovascular disease, 3%; diabetic retinopathy, 18%; neuropathy, 9%. | 8.7±7.1 | 39 | 37 | 11 | 47 | 39 | 5 | 0.593 | ||
| Xiao 2006 [34] | Chinese | 41/73 | No nephropathy, cerebrovascular disease, coronary heart disease or peripheral vascular disease | NR | 8 | 31 | 2 | 47 | 25 | 1 | 0.439 | ||
| Xu 2003 [34] | Chinese | 54/52 | No diabetic nephropathy | 6.77±4.08 | 24 | 21 | 9 | 20 | 25 | 7 | 1.000 | ||
| Wang 2001 [42] | Chinese | 117/85 | No overt nephropathy | 5.42±3.81 | 57 | 48 | 12 | 37 | 38 | 10 | 1.000 | ||
| Wen 2008 [32] | Chinese | 59/57 | No nephropathy | 4.8±5.3 | 21 | 32 | 6 | 27 | 25 | 5 | 1.000 | ||
| Yang 2001 [41] | Chinese | 102/62 | No diabetic nephropathy, diabetic retinopathy, and other microvascular complications | >10 | 32 | 56 | 14 | 26 | 28 | 8 | 1.000 | ||
| Yilmaz 2004 [22] | Turkish | 249/214 | Left ventricular hypertrophy present in 11.2% of cases | 9.5±7.7 | 121 | 98 | 30 | 101 | 93 | 20 | 1.000 | ||
| Yue 2006 [35] | Chinese | 140/30 | No diabetic nephropathy, diabetic retinopathy, or other microvascular complications | NR | 43 | 76 | 21 | 17 | 11 | 2 | 1.000 | ||
| Zhang 2002 [40] | Chinese | 100/100 | No macroangiopathy complications | NR | 32 | 55 | 13 | 40 | 49 | 11 | 0.662 | ||
| Zhang 2010 [30] | Chinese | 206/194 | NR | NR | 73 | 98 | 35 | 53 | 103 | 38 | 0.388 | ||
| Zhou 2004 [38] | Chinese | 67/69 | No macroangiopathy complications | NR | 5 | 42 | 20 | 8 | 31 | 30 | 1.000 | ||
| Caucasian | |||||||||||||
| Beneš 2001 [53] | Czech | 49/209 | No coronary artery disease | NR | 24 | 20 | 5 | 86 | 106 | 17 | 0.062 | ||
| Blüthner 1999 [55] | German and Polish | 146/150 | No diabetic nephropathy | 17.0±7.0 | 63 | 65 | 18 | 67 | 68 | 15 | 0.853 | ||
| Cenerelli 2002 [52] | Italy | 30/43 | No diabetic retinopathy, neuropathy, nephropathy, cardiovascular disease or coronary heart disease | 3.1±6.5 | 8 | 14 | 8 | 13 | 21 | 9 | 1.000 | ||
| Helfenstein 2005 [57] | Brazilian | 50/56 | No atherosclerosis, myocardial infarction, or diabetic retinopathy | NR | 26 | 20 | 4 | 26 | 24 | 6 | 1.000 | ||
| Książek 2004 [50] | Polish | 155/170 | No diabetic nephropathy. Retinopathy present in 8.4% of cases. | 9.8±5.1 | 82 | 58 | 15 | 71 | 83 | 16 | 0.304 | ||
| Mazza 2005 [54] | Italian | 105/120 | No coronary artery disease, cerebrovascular disease, kidney dysfunction, or diabetic proliferative retinopathy | 11.4±8.0 | 35 | 47 | 23 | 35 | 66 | 19 | 0.264 | ||
| Russo 2008 [49] | Italian | 90/91 | No cardiovascular disease | NR | 28 | 42 | 20 | 23 | 50 | 18 | 0.403 | ||
| Soares 2008 [56] | Brazilian | 7/16 | No coronary disease, stroke, or chronic renal failure | >1 | 5 | 2 | 0 | 9 | 5 | 2 | 0.530 | ||
| Wirta 2002 [51] | Finnish | 81/114 | Background retinopathy present in 3.6% of cases | 3 mos. (range, 1–11 mos.) | 44 | 29 | 8 | 60 | 47 | 7 | 0.811 | ||
| African | |||||||||||||
| Benrahma 2012 [58] | Moroccan | 282/262 | Neuropathic complications present in 30.5% of cases; cardiovascular complications, 17.4%; nephropathic complications, 2.5%. | NR | 160 | 97 | 25 | 114 | 122 | 26 | 0.487 | ||
| Mackawy 2011 [59] | Egyptian | 40/40 | No history of ischemic stroke | NR | 24 | 10 | 6 | 32 | 6 | 2 | 0.090 | ||
| Mehri 2010 [60] | Tunisian | 115/116 | History of cardiovascular disease present in 8.7% of cases; nephropathy, 26.1%; retinopathy, 26.1%; neuropathy, 19.1%. | 9.3±5.7 | 50 | 49 | 16 | 66 | 38 | 12 | 0.095 | ||
| Mtiraoui 2007 [8] | Tunisian | 267/400 | No nephropathy. Neuropathy present in 23.6% of cases; retinopathy, 19.1%. | 12.3±4.1 | 152 | 79 | 36 | 270 | 94 | 36 | <0.001 | ||
Abbreviations: NR, not reported; T2DM, type 2 diabetes mellitus; PCR-RFLP, polymerase chain reaction assay based on restriction fragment length polymorphism.
a
Defined as serious complications aside from the more frequent clinical manifestations of T2DM such as hyperlipidaemia, hypertension and obesity.
b
Reported as either “median (range)” or as “mean ± standard deviation”, unless indicated otherwise.
c
P value for Hardy-Weinberg equilibrium for rs1801133 genotype among controls.