Table 1 Genes/loci and their variants investigated in the reviewed articles and their association with acne presentation and severity
Gene | Chromosomal location‡ | Common name of variant | rs number | Most severe consequence | eQTL availability for the associated gene in column 1 (from GTex Portal); tissue type | Phenotype | Association? | Population | Size of study (case/control) | Genotype/allele: OR (CI); p value | Authors, year of publication (Reference) |
|---|---|---|---|---|---|---|---|---|---|---|---|
Genes involved in inflammatory and immune responses | |||||||||||
ACE | 17q23 | ID VNTR | – | Intron | No | Acne | Yes | Egypt | 100/120 | ID: 1.780 (1.086–2.918); 0.022 DD: 3.735 (2.289–6.097); < 0.001 D: 3.581 (2.376 5.397); < 0.001 | Sorour et al. [17] |
IL1A | 2q14.1 | − 889 C/T | rs1800587 | Promoter | Yes; Nerve—Tibial, Spleen | Acne | Yes | Poland | 115/100 | TT: 3.77 (1.02–13.85); 0.044 T: 1.386 (0.909–2.112); 0.129 | Sobjanek et al. [18] |
Acne | Yes | Pakistan | 430/380 | TT: 2.62 (1.98–3.5); < 0.0001 T: 2.012 (1.605–2.524); < 0.0001 | Younis and Javed, [19] | ||||||
Acne | Yes | Greece | 100/100 | TT: 4.818 (1.959–11.847); < 0.001 T: 1.704 (1.134–2.561); < 0.01 | Ibrahim et al. [20] | ||||||
+ 4845/ + 340 G/T (Ala114Ser) | rs17561 | Coding region; missense | Yes; Spleen, Nerve—Tibial | Acne | Yes | Hungary and Romania | 229/127 | Not reported | Szabó et al. [21] | ||
Severe acne | No | USA | 81/847 | OR, CI not reported; p-value reported as “not significant” | Zhang et al. [12] | ||||||
IL1RN | 2q14.1 | 86 bp VNTR | – | Intron | No | Acne | No | Hungary and Romania | 229/127 | Not reported | Szabó et al. [21] |
IL1B | 2q14.1 | − 511 C/T | rs16944 | Intergene | Yes; Testis | Acne, acne severity and acne scarring | No | Turkey | 90/30 | Not reported | Akoglu et al. [22] |
IL4R | 16p12.1 | A/G (Gln551Arg) | rs1801275 | Coding region; missense | No | Acne | Yes | Saudi Arabia | 95/93 | GG (vs. GA + AA): 8.5 (3.6–20.4); < 0.001 G: 2.7 (1.7–4.2); < 0.001 | Al Robaee et al. [23] |
Acne severity | No | Saudi Arabia | 95/93 | Not reported | Al Robaee et al. [23] | ||||||
IL4 | 5q31.1 | − 590 T/C | rs2243250 | Promoter | Yes; Pituitary, Testis, Lung | Acne and acne severity | No | Saudi Arabia | 95/93 | Not reported | Al Robaee et al. [23] |
IL10 | 1q32.1 | − 1082 A/G | rs1800896 | Promoter | No | Acne and acne severity | No | Saudi Arabia | 166/390 | Not reported | Al-Shobaili et al. [24] |
ITLN1 | 1q23.3 | + 326 A/T (Val109Asp) | rs2274907 | Coding region; missense | Yes; Minor Salivary Gland, Testis, Whole Blood | Acne | No | Turkey | 65/44 | Val/Asp: 0.696 (0.310–1.564); 0.381 Val/Val: 1.839 (0.442–7.653); 0.403 Val/Asp + Val/Val: 0.834 (0.386–1.800); 0.643 | Soguktas, et al. [25] |
IL17A | 6p12.2 | – | rs2275913 | Intergene | No | Severe acne, Acne as teenager | No | USA | 22,616/247,345 | A: 1.0062 (0.9858,1.0271); 0.554 OR not available for acne as teenager phenotype | Ehm et al. [26] |
IL17F | 6p12.2 | His161Arg | rs763780 | Coding region; missense | No | Severe acne, Acne as teenager | No | USA | 22,616/247,345 | C: 1.0 (0.9548,1.0 74); 0.999 OR not available for acne as teenager phenotype | Ehm et al. [26] |
IL17RB | 3p21.1 | Gln484Stop | rs1043261 | Coding region; stop gained | Yes; Thyroid | Severe acne, Acne as teenager | No | USA | 22,616/247,345 | T: 0.9738 (0.9391,1.0098); 0.151 OR not available for acne as teenager phenotype | Ehm et al. [26] |
IL23R | 1p31.3 | Arg381Gln | rs11209026 | Coding region; missense | No | Severe acne, Acne as teenager | No | USA | 22,616/247,345 | A: 0.9790 (0.9414,1.0181); 0.288 OR not available for acne as teenager phenotype | Ehm et al. [26] |
MAPK11, OVOL1 | 22q13.33 | – | rs144991069 | Intergene | No | Severe acne | Yes | UK | 3,823/16,144 | A: 1.85 (1.50–2.28); 1.01 × 10−8 | Petridis et al. [11] |
MMP2 | 16q12.2 | − 1306 C/T | rs2285053 | Promoter | No | Acne | No | Turkey | 43/42 | CT: 0.75 (0.3–1.86); 0.532 TT: 0.42 (0.06–2.91); 0.381 CT + TT: 0.7 (0.29–1.69); 0.427 | Yaykasli et al. [27] |
Acne | Yes | China | 251/121 | CT: 0.285 (0.154–0.529); < 0.001 TT: 0.614 (0.559–0.674); 0.171 CT + TT: 0.275 (0.148–0.509); < 0.001 T: 0.306 (0.170–0.550); < 0.001 | Gao et al. [28] | ||||||
Acne severity | No | China | 251/121 | Not reported | Gao et al. [28] | ||||||
NLRP3 | 1q44 | – | rs10754558 | 3′ UTR | No | Acne | Yes | China | 428/384 | G: 1.22 (1.00–1.48); < 0.05 | Shen et al. [29] |
– | rs4612666 | Intron | No | Acne | No | China | 428/384 | T: 1.05 (0.86–1.28); 0.64 | Shen et al. [29] | ||
RETN | 19p13.2 | − 420 C/G | rs1862513 | Promoter | No | Acne and acne severity | Yes | Pakistan | 180/180 | G: 1.8 (1.23–2.89); 0.002 | Hussain et al. [29] |
Acne and acne severity | Yes | Pakistan | 530/550 | G: 1.24 (1.05–1.47); 0.013 | Younis et al. [30] | ||||||
+ 299 G/A | rs3745367 | Intron | No | Acne and acne severity | Yes | Pakistan | 530/550 | A: 1.314 (1.10–1.57); 0.002 | Younis et al. [30] | ||
− 420/299 haplotype | rs1862513, rs3745367 | Promoter, intron | No | Acne | Yes | Pakistan | 530/550 | G–A: 1.61 (1.29–2.03); 0.0001 | Younis et al. [30] | ||
SELL | 1q24.2 | – | rs7531806 | Intron | Yes; Brain—Putamen (basal ganglia), Brain—Caudate (basal ganglia), Brain—Cortex | Severe acne | Yes | China | GWAS: 1,056/1,056 Replication: 1,860/3,660 Combined: 2,916/4,716 | A allele GWAS: 1.20 (1.06–1.36); 3.54 × 10−3 Replication: 1.23 (1.13–1.34); 9.22 × 10−7 Combined: 1.22 (1.12–1.28); 1.20 × 10−8 | He et al. [9] |
Severe acne | No | UK | 1,893/5132 | A: 1.0292 (0.9852–1.0752); 0.197 | Navarini et al. [10] | ||||||
Severe acne | No | UK | 3,823/16,144 | A: 1.03 (0.98–1.07); 0.206 | Petridis et al. [11] | ||||||
SEMA4B | 15q26.1 | – | rs34560261 | Intron | Yes; Skin—Not Sun Exposed (Suprapubic, Skin—Sun Exposed (Lower leg), Esophagus—Mucosa | Severe acne | Yes | UK | 3,823/16,144 | C: 1.35 (1.24–1.47); 1.82 × 10−12 | Petridis et al. [11] |
– | rs1533326 | Intron | No | Severe acne | Yes | UK | 3,823/16,144 | A: 1.08 (1.03–1.13); 0.00308 | Petridis et al. [11] | ||
TIMP2 | 17q25.3 | − 418 G/C | rs8179090 | Promoter (transcription factor binding site) | No | Acne | No | Turkey | 43/42 | GC: 0.581 (0.21–1.58); 0.29 CC: 1.45 (0.23–8.87); 0.686 GC + CC: 0.7 (0.28–1.76); 0.451 | Yaykasli et al. [27] |
Acne and acne severity | No | China | 251/121 | For acne only (severity not reported) GC: 1.220 (0.737–2.021); 0.439 CC: 2.082 (0.573–7.569); 0.256 GC + CC: 1.301 (0.802–2.110); 0.285 C: 1.327 (0.869–2.027); 0.189 | Gao et al. [28] | ||||||
TLR2 | 4q31.3 | + 2179 C/T or + 2029 C/T (Arg677Trp) | rs121917864 | Coding region; missense | No | Acne | No | Hungary | 63/38 | SNP not detected | Koreck et al. [31] |
+ 2258 G/A (Arg753Gln) | rs5743708 | Coding region; missense | No | Acne | No | Hungary | 63/38 | SNP not detected | Koreck et al. [31] | ||
Severe acne | No | USA | 81/847 | Not reported (not in dataset) | Zhang et al. [12] | ||||||
Acne and acne severity | Yes | China | Gln/Gln: 2.261 (1.052–4.858); 0.034 | Tian et al. [32] | |||||||
TLR4 | 9q33.1 | + 1063 A/G (Asp299Gly) | rs4986790 | Coding region; missense | No | Acne | No | Hungary | 63/38 | Not reported | Koreck et al. [31] |
Severe acne | No | USA | 81/847 | Not reported | Zhang et al. [12] | ||||||
+ 1363 C/T (Thr399Ile) | rs4986791 | Coding region; missense | No | Acne | No | Hungary | 63/38 | Not reported | Koreck et al. [31] | ||
Severe acne | No | USA | 81/847 | Not reported | Zhang et al. [12] | ||||||
– | 15 SNPs (full list in Additional file 2) | 3′ UTR | Please refer to Additional file 2: Table S2.2 | Acne | Yes | Singapore | 982/846 | Please refer to Additional file 2: Table S2.2 | Our unpublished data, 2020 | ||
TNF | 6p21.33 | − 238 G/A | rs361525 | Promoter | No | Acne and acne severity | Yes | Pakistan | 140/160 | A: 1.6 (1.06–2.44); < 0.03 GA + AA Mild: 0.677 (0.353–1.3); 0.241 Moderate: 2.00 (0.798–5.015); 0.139 Severe: 2.678 (1.405–5.104); 0.003 | Aisha et al. [33] |
Acne | No | Poland | 84/75 | A: 1.358 (0.472–3.911);0.57 | Sobjanek et al. [34] | ||||||
Acne and acne severity | No | Hungary and Romania | 224/112 | A: 1.29 (0.57–2.91); 0.539 GA + AA Mild, moderate, severe: OR could not be computed as GA + AA for controls is 0 | Szabó et al. [35] | ||||||
− 308 G/A | rs1800629 | Promoter | No | Acne and acne severity | Yes | Pakistan | 140/160 | A: 1.5 (1.07–2.19); 0.02 GA + AA Mild: 0.5 (0.278–0.901); 0.021 Moderate: 2.364 (1.094–5.105); 0.029 Severe: 10.333 (3.036–35.174); < 0.001 | Aisha et al. [33] | ||
Acne, acne severity and acne scarring | No | Turkey | 90/30 | A: 0.547 (0.277–1.079);0.082 GA + AA Mild: 0.737 (0.233–2.332); 0.603 Moderate: 0.571 (0.175–1.865); 0.354 Severe: 0.643 (0.221–1.87); 0.417 | Akoglu et al. [22] | ||||||
Acne | Yes | Saudi Arabia | 166/390 | 0.879 (0.636–1.216);0.436 | Al-Shobaili et al. [24] | ||||||
Acne severity | No | Saudi Arabia | 166/390 | GA + AA vs GG Mild:0.698 (0.328–1.488); 0.352 Moderate: 1.047(0.581–1.888);0.878 Severe: 1.257 (0.643–2.455); 0.504 | Al-Shobaili et al. [24] | ||||||
Acne | Yes | Turkey | 113/114 | A: 4.138 (2.25–7.612); < 0.0001 | Baz et al. [36] | ||||||
Acne severity | No | Turkey | 113/114 | GA + AA Mild: 6.6 (2.737–15.918); < 0.0001 Moderate: 3.3 (1.489–7.316); 0.003 Severe: 5.775 (2.349–14.199); < 0.0001 | Baz et al. [36] | ||||||
Acne | No | Greece | 185/165 | A: 1.684 (0.914–3.102);0.095 | Grech et al. [37] | ||||||
Acne | No | Poland | 85/75 | A: 0.616 (0.329–1.151);0.129 | Sobjanek et al. [34] | ||||||
Acne | Yes (females); No (males, total population) | Hungary and Romania | 224/112 | A: 1.455 (0.935–2.265);0.097 | Szabó et al. [35] | ||||||
Acne severity | No | Hungary and Romania | 224/112 | GA + AA Mild: 1.379 (0.569–3.341); 0.477 Moderate: 1.532 (0.907–2.589); 0.111 Severe: 1.585 (0.754–3.334); 0.225 | Szabó et al. [35] | ||||||
Acne | No | USA | 81/847 | Not reported | Zhang et al. [12] | ||||||
− 857 C/T | rs1799724 | Promoter | No | Acne and acne severity | Yes | Hungary and Romania | 224/112 | CT + TT: 1.79 (1.14–2.81); 0.010 | Szabó et al. [35] | ||
Severe acne | No | USA | 81/847 | Not reported | Zhang et al. [12] | ||||||
− 863 C/A | rs1800630 | Promoter | No | Acne and acne severity | No | Hungary and Romania | 224/112 | CA + AA: 0.93 (0.54–1.59); 0.781 | Szabó et al. [35] | ||
− 1031 T/C | rs1799964 | Promoter | No | Acne and acne severity | No | Hungary and Romania | 224/112 | TC + CC: 1 (0.61–1.63); 1 | Szabó et al. [35] | ||
− 238 G/A, − 308 G/A, − 376 G/A haplotype | rs361525, rs1800629, rs1800750 | Promoter | No | Acne | No | Greece | 185/165 | Not reported | Grech et al. [37] | ||
TNFRSF1B | 1p36.22 | Met196Arg | rs1061622 | Coding region; missense | No | Acne and acne severity | Yes | China | 93/90 | M/R + R/R: 1.899 (1.036–3.445); 0.037 | Tian et al. [32] |
Severe acne | No | USA | 81/847 | Not reported | Zhang et al. [12] | ||||||
TRAF3IP2 | 6q21 | Asp10Asn | rs33980500 | Coding region; synonymous | Yes; Cells—Cultured fibroblasts | Severe acne | Yes | USA | 22,616/247,345 | Asn: 0.93 (0.89,0.96); 0.000059 | Ehm et al. [26] |
Acne as teenager | No | USA | 22,616/247,345 | OR not available for acne as teenager phenotype | Ehm et al. [26] | ||||||
TYK2 | 19p13.2 | Ile684Ser | rs12720356 | Coding region; missense | Yes; Whole Blood, Adrenal Gland | Acne as teenager | Yes | USA | 22,616/247,345 | OR not available for acne as teenager phenotype; p = 0.000105 | Ehm et al. [26] |
Genes involved in sebaceous gland function and activity | |||||||||||
ADH7 | 4q23 | – | rs1154469 | Splice region | No | Severe acne | Yes | China | 1,024/1,029 | T: 1.111 (1.001–1.233) 4.85 × 10−2 | Yang et al. [38] |
AR | Xq12 | CAG (Gln) repeat VNTR | – | Coding region; Exon 1 | No | Acne | Yes | China | 238/207 | CAG < 23 Males: 2.07 (1.21–3.54); 0.008 Females: 2.05 (1.18–3.56); 0.013 | Pang et al. [39] |
Acne and acne severity | Yes (males); No (females) | China | 206/200 | Genotype/allele frequency not reported Mean CAG repeat length in males: 22.07 ± 3.026 control vs 20.61 ± 2.423 cases; p < 0.001 | Yang et al. [40] | ||||||
Acne | No (overall, males) Yes (female) | Turkey | 100/99 | Genotype/allele frequency not reported Mean CAG repeat length: case 19.34 (20.22 in males and 18.88 in females) vs. control 19.7 (19.18 for males and 19.96 for females); p > 0.05 for overall & p = 0.0059 among females | Demirkan et al. [41] | ||||||
Acne | No (both males & females) | USA mixed (Caucasians, African, Hispanic) | 12/12 | Genotype and allele frequency not reported Mean CAG repeat length: case 20 ± 3 vs. control 20 ± 3; p = 0.27 | Sawaya and Shalita [42] | ||||||
GGN (Gly) repeat VNTR | – | Coding region; Exon 1 | No | Acne | No | China | 237/205 | GGN ≤ 23 Males: 1.75 (0.72–4.26); 0.264 Females: 0.90 (0.39–2.08); 0.83 | Pang et al. [39] | ||
CYP17A1 | 10q24.32 | − 34 T/C | rs743572 | 5′ UTR/Promoter | Yes; Thyroid, Adipose—Subcutaneous, Nerve—Tibial | Acne and acne severity | Yes | Iran | 198/195 | T Overall: 2.31 (1.47–3.64); < 0.001 Mild: 2.35 (1.37–4); 0.001 Moderate: 2.06 (1.08–3.92); 0.03 Severe: 2.52 (1.37–4.63); < 0.01 | Chamaie-Nejad et al. [43] |
Severe acne | No | USA | 81/847 | Not reported | Zhang et al. [12] | ||||||
Acne and acne severity | Yes | Uzbekistan | 165/97 | T Overall: 3.14 (2.07–4.76); < 0.05 Mild: 0.788 (0.43–1.444); 0.44 Severe: 15.05 (8.014–28.27); < 0.05 Moderate: 3.4 (2.07–5.39); < 0.05 | Malikova et al. [44] | ||||||
Acne | No (Males) Yes (Overall) | China | 206/200 | T: 0.722 (0.548–0.951); 0.021 | He et al. [45] | ||||||
Acne severity | Yes (Males); No (females) | China | 206/200 | T Mild + Moderate: 0.931 (0.633–1.307);0.68 Severe: 0.562 (0.401–0.789); 0.001 | He et al. [45] | ||||||
CYP19A1 | 15q21.2 | Trp39Arg | rs2236722 | Coding region; missense | No | Acne and acne severity | Yes | Iran | 198/195 | C Overall: 2.03 (1–4.12); < 0.05 Mild: 3.0 (1.33–6.71); < 0.01 | Chamaie-Nejad et al. [43] |
rs700518 | Coding region; synonymous | Yes; Whole Blood, Cells—Cultured fibroblasts, Skin—Sun Exposed (Lower leg) | Acne and acne severity | Yes | Iran | 181/144 | A Overall: 1.71 (1.25–2.34); 0.001 Mild: 1.64 (1.1–2.43); 0.014 Moderate: 1.67 (1.05–2.66); 0.03 Severe: 1.6 (1.02–2.51); 0.042 | Ebrahimi et al. [46] | |||
CYP1A1 | 15q22–q24 | + 6235 T/C | rs4646903 | Intergene | Yes; Brain—Nucleus accumbens (basal ganglia) | Acne | No | Indonesia | 35/35 | C: 0.738 (0.372–1.464);0.384 | Darmani et al. [47] |
Acne | No | Germany | 96/408 | C: 1.21 (0.68–2.16); 0.52 | Paraskevaidis et al. [48] | ||||||
+ 4889 A/G (Ile462Phe/Val/Leu) | rs1048943 | Coding region; missense | No | Acne | No | Germany | 96/408 | G: 1.02 (0.41–2.52); 0.96 | Paraskevaidis et al. [48] | ||
DDB2 | 11p11.2 | – | rs747650 | Intron | Yes; Skin—Not Sun Exposed (Suprapubic), Skin—Sun Exposed (Lower leg), Esophagus—Mucosa, Adipose—Subcutaneous, Muscle—Skeletal, Heart—Atrial Appendage | Severe acne | Yes | China | GWAS: 1,056/1,056 Replication: 1,860/3,660 Combined: 2,916/4,716 | G allele GWAS: 1.29 (1.14–1.47); 8.12 × 10−5 Replication: 1.22 (1.12–1.33); 9.25 × 10−6 Combined: 1.24 (1.16–1.34) 4.41 × 10−9 | He et al. [9] |
Severe acne | No | UK | 1,893/5,132 | G: 0.9886 (0.945–1.0342); 0.6188 | Navarini et al. [10] | ||||||
Severe acne | No | UK | 3,823/16,144 | G: 1.01 (0.97–1.06); 0.601 | Petridis et al. [11] | ||||||
– | rs1060573 | Intron | Yes; Skin—Not Sun Exposed (Suprapubic), Skin—Sun Exposed (Lower leg), Esophagus—Mucosa, Adipose—Subcutaneous, Muscle—Skeletal, Heart—Atrial Appendage | Severe acne | Yes | China | GWAS: 1,056/1,056 Replication: 1,860/3,660 Combined: 2,916/4,716 | G allele GWAS: 1.29 (1.14–1.47); 9.00 × 10−5 Replication: 1.20 (1.10–1.31); 2.44 × 10−5 Combined: 1.23 (1.15–1.33); 1.28 × 10−8 | He et al. [9] | ||
FST | 5q11.2 | – | rs38055 | Intergene | No | Severe acne | Yes | UK | Discovery: 1,893/5,132 2nd stage: 2,207/2,087 | A allele Discovery: 1.17 (1.08–1.27); 6.02 × 10−5 2nd Stage:1.24 (1.13–1.36); 1.03 × 10−5 Pmeta: 4.58 × 10−9 | Navarini et al. [10] |
Severe acne | Yes | UK | 3823/16,144 | A: 1.19 (1.14–1.24); 1.57 × 10−14 | Petridis et al. [11] | ||||||
rs629725 | Promoter (transcription factor binding site) | No | Severe acne | Yes | UK | 3823/16,144 | T: 1.20 (1.14–1.27); 8.22 × 10−12 | Petridis et al. [11] | |||
IGF1 | 12q23.2 | CA repeat VNTR | – | 5′ UTR/Promoter | No | Acne | No | Egypt | 50/50 | 192/192: 2.708 (0.668–10.983); 0.163 | El-Tahlawi et al. [49] |
Acne severity | No | Egypt | 50/50 | Not reported | El-Tahlawi et al. [49] | ||||||
Acne and acne severity | Yes | India | 80/80 | 192/192: 4.29 (1.38–13.33); 0.01 | Rahaman et al. [50] | ||||||
Acne and acne severity | Yes | Turkey | 115/117 | 192/192: 0.875 (0.336–2.281); 0.785 | Tasli et al. [51] | ||||||
HSD11B1 | 1q32.2 | – | rs12086634 | Intron | No | Acne | No | Egypt | 50/50 | A: 3.197 (0.839–12.18); 0.088 | Farag et al. [52] |
– | rs846910 | Intron | No | Acne | Yes | Egypt | 50/50 | G: 3.296 (1.61–6.748); 0.001 | Farag et al. [52] | ||
Acne severity | No | Egypt | 50/50 | Not reported | Farag et al. [52] | ||||||
HSD3B1 | 1p12 | – | rs6428829 | Intron | No | Acne | Yes | China | 403/207 | G: 1.963 (1.206–3.197); 0.006 | Yang et al. [53] |
Ile79Val | rs6201 | Missense | No | Acne | No | China | 403/207 | G: 0.938 (0.49–1.795) 0.846 | Yang et al. [53] | ||
Leu338Val | rs6203 | Missense | No | Acne | No | China | 403/207 | T: 0.92 (0.717–1.18) 0.511 | Yang et al. [53] | ||
Ile79Val, Leu338Val, – | rs6201, rs6203, rs6428829 haplotype | Coding region; missense, Coding region; missense, Intron | No | Acne | Yes | China | 403/207 | AAT: 0.653 (0.627–0.681); 0.00001 | Yang et al. [53] | ||
HSD17B3 | 9q22.32 | – | rs2257157 | Intron | No | Acne | No | China | 403/207 | G: 0.874 (0.678–1.126) 0.297 | Yang et al. [53] |
– | rs7039978 | Intron | Yes; Nerve—Tibial, Adipose—Subcutaneous, Thyroid | Acne | No | China | 403/207 | G: 0.804 (0.626–1.033) 0.087 | Yang et al. [53] | ||
– | rs2476923 | Intron | Yes; Nerve—Tibial, Adipose—Subcutaneous, Thyroid | Acne | No | China | 403/207 | G: 0.867 (0.681–1.103) 0.245 | Yang et al. [53] | ||
– | rs11788785 | Intron | Yes; Adipose—Subcutaneous | Acne | No | China | 403/207 | G: 1.173 (0.924–1.489) 0.19 | Yang et al. [53] | ||
Gly289Cys/Arg/Ser | rs2066479 | Missense | Yes; Nerve—Tibial, Heart—Atrial Appendage | Acne | No | China | 403/207 | G: 1.086 (0.821–1.437) 0.562 | Yang et al. [53] | ||
– | rs8190557 | Intron | Yes; Nerve—Tibial, Heart—Atrial Appendage | Acne | No | China | 403/207 | G: 1.098 (0.829–1.456) 0.514 | Yang et al. [53] | ||
– | rs10990258 | Intron | Yes; Thyroid | Acne | No | China | 403/207 | G: 1.102 (0.848–1.433) 0.466 | Yang et al. [53] | ||
– | rs11788083 | Intron | No | Acne | No | China | 403/207 | G: 0.827 (0.641–1.066) 0.142 | Yang et al. 2013 [53] | ||
– | rs8190504 | Intron | Yes; Small Intestine—Terminal Ileum | Acne | No | China | 403/207 | G: 0.859 (0.645–1.145) 0.3 | Yang et al. [53] | ||
– | rs2066476 | 5′ UTR | Yes; Small Intestine—Terminal Ileum | Acne | No | China | 403/207 | G: 0.997 (0.736–1.349) 0.983 | Yang et al. [53] | ||
– | rs4743709 | 5′ UTR | Yes; Pancreas, Cells—Cultured fibroblasts, Colon—Transverse, Small Intestine—Terminal Ileum, Liver, Adipose—Visceral (Omentum), Artery—Tibial, Adipose—Subcutaneous, Skin—Not Sun Exposed (Suprapubic) | Acne | No | China | 403/207 | G: 0.929 (0.72–1.199) 0.572 | Yang et al. [53] | ||
H8 haplotype | n/a | n/a | n/a | Acne | Yes | China | 403/207 | GGAAGGAAAA: 0.469 (0.296–0.744); 0.00185 | Yang et al. [53] | ||
LAMC2 | 1q25.3 | – | rs10911268 | Intergene | Yes; Nerve—Tibial, Brain—Cortex, Brain—Anterior cingulate cortex (BA24), Brain—Frontal Cortex (BA9), Adipose—Subcutaneous, Pituitary, Esophagus—Muscularis, Brain—Hypothalamus, Colon—Sigmoid, Heart—Atrial Appendage | Severe acne, | Yes | UK | 3,823/16,144 | C: 1.19 (1.13–1.25); 2.44 × 10−10 | Petridis et al. [11] |
LGR6 | 1q32.1 | – | rs788790 | Intergene | Yes; Testis, Heart—Atrial Appendage, Skin—Sun Exposed (Lower leg) | Severe acne | Yes | UK | 3,823/16,144 | C: 1.12 (1.06–1.17); 1.96 × 10−5 | Petridis et al. [11] |
MUC1 | 1q22 | 20 aa VNTR | – | Coding region | No | Severe acne | Yes | Japan | 67/64 | Not reported | Ando et al. [54] |
OVOL1 | 11q13.1 | – | rs478304 | Promoter | Yes; Thyroid, Brain—Cerebellum, Brain—Cerebellar Hemisphere, Brain—Cortex | Severe acne | Yes | UK | Discovery: 1,893/5,132 2nd stage: 2,207/2,087 | T allele Discovery: 1.20 (1.11–1.29); 9.58 × 10−6 2nd stage: 1.26 (1.16–1.38); 2.65 × 10−7 Pmeta: 3.23 × 10−11 | Navarini et al. [10] |
Severe acne | Yes | UK | 3,823/16,144 | T: 1.14 (1.09–1.19); 2.14 × 10−9 | Petridis et al. [11] | ||||||
– | rs144991069 | Intergene | No | Severe acne | Yes | UK | 3,823/16,144 | A: 1.85 (1.50–2.28); 1.01 × 10−8 | Petridis et al. [11] | ||
rs61744384 | Coding region; synonymous | No | Severe acne | Yes | UK | 3,823/16,144 | T: 1.16 (1.11–1.21); 2.95 × 10−11 | Petridis et al. [11] | |||
PPARG | 3p25.2 | P12A | rs1801282 | Coding region; missense | Yes, Esophagus—Mucosa, Esophagus—Gastroesophageal Junction, Cells—EBV-transformed lymphocytes, Esophagus—Muscularis | Acne and acne severity | Yes | Egypt | 100/100 | G: 2.103 (1.262–3.503); 0.004 | Amr et al. 2014 [55] |
Acne | Yes (for patients with age of acne onset ≥ 20 years); No (overall population) | Iran | 198/195 | G: 1.444 (0.911–2.287);0.118 | Saeidi et al. [56] | ||||||
Acne severity | No | Iran | 198/195 | Not reported | Saeidi et al. [56] | ||||||
– | rs3856806 | Coding region; synonymous | No | Acne and acne severity | No | Iran | 198/195 | Not reported | Saeidi et al. [56] | ||
SPECC1L | 22q11.23 | – | rs28360612 | Intron | Yes; Skin—Sun Exposed (Lower leg), Artery—Tibial, Artery—Aorta, Cells—Cultured fibroblasts, Muscle—Skeletal, Adipose—Subcutaneous, Skin—Not Sun Exposed (Suprapubic) | Severe acne | Yes | UK | 3,823/16,144 | T: 1.16 (1.09–1.23); 7.12 × 10−7 | Petridis et al. [11] |
SRD5A2 | 2p23.1 | TA repeat VNTR | – | 3′ UTR | No | Acne | Yes | China | 49/50 | L: 3.52 (1.73–7.16); < 0.005 | Hu et al. [57] |
V89L | rs523349 | Coding region; missense | No | Acne | No | China | 49/50 | Not reported | Hu et al. [57] | ||
VDR | 12q13.11 | TaqI | rs731236 | Coding region; synonymous | Yes; Testis | Acne | Yes | Egypt | 30/30 | Not reported | Swelam et al. [57] |
ApaI | rs7975232 | Intron | Yes; Testis | Acne | Yes | Egypt | 30/30 | Not reported | Swelam et al. [58] | ||
Acne severity | No | Egypt | 30/30 | Not reported | Swelam et al. [58] | ||||||
WNT10A | 2q35 | Phe228Ile | rs121908120 | Coding region; missense | No | Severe acne | Yes | UK | 3823/16,144 | T: 2.10 (1.67–2.63); 1.40 × 10−10 | Petridis et al. [11] |
rs72966077 | Intron | No | Severe acne | Yes | UK | 3,823/16,144 | C: 1.33 (1.19–1.48); 4.23 × 10−7 | Petridis et al. [11] | |||
Genes involved in both inflammatory and immune responses and sebaceous gland function and activity | |||||||||||
EGFR | 7p11.2 | D994D | rs2293347 | Coding region; synonymous | No | Acne | No | Turkey | 156/154 | T: 0.8092 (0.5049 –1.297); 0.3782 | Aydingoz et al. [59] |
R521K | rs2227983 | Coding region; missense | No | Acne | No | Turkey | 156/154 | A: 1.055 (0.7227–1.541); 0.7802 | Aydingoz et al. [59] | ||
CA repeat intron 1 VNTR | Intron | No | Acne | No | Turkey | 156/154 | Genotype/allele frequency not reported CA repeat mean length: Acne 16.49 ± 1.769 vs. control 16.56 ± 1.844; p = 0.6818 | Aydingoz et al. [59] | |||
IL6 | 7p15.3 | − 572 G/C | rs1800796 | Promoter | No | Acne | Yes | Egypt | 30/20 | C: 5.44 (2.27–13.04); < 0.001 | Ragab et al. [60] |
Acne severity | No | Egypt | 30/20 | Not reported | Ragab et al. [60] | ||||||
Acne | Yes | Pakistan | 430/380 | C: 2.011 (1.61–2.45); < 0.0001 | Younis and Javed [19] | ||||||
IL8 | 4q13.3 | − 251 T/A | rs4073 | Promoter | No | Acne and acne severity | Yes | Pakistan | 264/264 | A: 1.6 (1.16–2.19); 0.003 | Hussain et al. [61] |
Acne | No | Poland | 115/100 | A: 1.074 (0.735–1.571); 0.711 | Sobjanek et al. [18] | ||||||
TGFB2 | 1q41 | – | rs1159268 | Promoter | Yes; Esophagus—Mucosa | Severe acne | Yes | UK | Discovery: 1,893/5,132 2nd stage: 2,207/2,087 | A allele Discovery: 1.17 (1.08–1.26); 3.34 × 10−6 2nd stage: 1.15 (1.05–1.26); 3.17 × 10−3 Pmeta: 4.08 × 10−8 | Navarini et al. [10] |
Severe acne | Yes | UK | 3,823/16,144 | A: 1.14 (1.09–1.19); 4.74 × 10−9 | Petridis et al. [11] | ||||||
rs1256580 | Intron | No | Severe acne | Yes | UK | 3,823/16,144 | C: 1.23 (1.15–1.31); 1.12 × 10−9 | Petridis et al. [11] | |||
rs6684868 | Promoter (Tf binding site) | Yes; Esophagus—Mucosa | Severe acne | Yes | UK | 3,823/16,144 | A: 1.15 (1.10–1.20); 2.42 × 10−10 | Petridis et al. [11] | |||
rs11118336 | Intergene | No | Severe acne | Yes | UK | 3,823/16,144 | C: 1.11 (1.06–1.16); 1.49 × 10−6 | Petridis et al. [11] | |||
Genes with other functions | |||||||||||
BCL11A | 2p16.1 | – | rs2901000 | Intergene | Yes; Esophagus—Mucosa | Severe acne | Yes | UK | 3823/16,144 | A: 1.16 (1.10–1.22); 2.53 × 10−8 | Petridis et al. [11] |
F13A1 | 6p25 | Val34Leu | rs435048 | Intron | No | Severe acne | Yes | China | 1,024/1,029 | 1.371 (1.164–1.616); 1.54 × 10−4 | Yang et al. [38] |
FGF2 | 4q28.1 | – | rs4487353 | Intergene | Yes; Nerve—Tibial | Severe acne | Yes | UK | 3,823/16,144 | G: 1.13 (1.07–1.19); 3.83 × 10−6 | Petridis et al. [11] |
GLI2 | 2q14.2 | – | rs1092479 | Intergene | No | Severe acne | Yes | UK | 3,823/16,144 | C: 1.12 (1.06–1.19); 3.60 × 10−5 | Petridis et al. [11] |
LINC00958 | 38p12 | – | rs2727365 | Intron | Yes; Esophagus—Mucosa, Thyroid, Whole Blood, Skin—Not Sun Exposed (Suprapubic) | Severe acne | Yes | UK | 3,823/16,144 | G: 1.19 (1.13–1.25); 1.08 × 10−10 | Petridis et al. [11] |
LOC105378977 | 5q11.2 | – | rs158639 | Intron | No | Severe acne | Yes | UK | 3,823/16,144 | A: 1.15 (1.09–1.21); 9.22 × 10−7 | Petridis et al. [11] |
RORC | 1q21.3 | – | rs4845604 | Intron | No | Severe acne, Acne as teenager | No | USA | 22,616/247,345 | A: 1.0023 (0.9740,1.0314); 0.876 | Ehm et al. [26] |
PINX1 | 8p23.1 | – | rs28570522 | Intron | No | Severe acne | Yes | UK | 3,823/16,144 | A: 1.14 (1.09–1.21); 4.206 × 10−7 | Petridis et al. [11] |
SUGCT | 7p14.1 | – | rs7809981 | Intron | Yes; Skin—Sun Exposed (Lower leg) | Severe acne | Yes | UK | 3,823/16,144 | T: 1.15 (1.08–1.22); 3.74 × 10−6 | Petridis et al. [11] |
n/a | 38p12 | – | rs4133274 | Non-coding exon | No | Severe acne | Yes | USA | 81/847 | G: 4.01 (2.37–6.82); 1.70 × 10−6 | Zhang et al. [12] |
n/a | 38p12 | – | rs13248513 | Intergene | No | Severe acne | Yes | USA | 81/847 | C: 3.82 (2.29–6.36) 2.02 × 10−6 | Zhang et al. [12] |