Authors Methylation Type Measurement method Study participants Findings Comments Age Agodi et al., 2015 [21 ] LINE-1 Pyrosequencing 177 women aged 13–50, Helsinki No differences Bollati et al., 2009 [22 ] LINE-1 Pyrosequencing 718 individuals aged 55–92 from the Boston Area Normative Aging Study No differences Chalitchagorn et al., 2004 [23 ] LINE-1 COBRA PCR 32 individuals ranging in age, Thailand No differences Duggan et al., 2014 [24 ] LINE-1 Pyrosequencing 300 overweight women aged 50–75 in the US No differences El-Maarri et al., 2011 [25 ] LINE-1 Pyrosequencing, SIRPH 500 individuals aged 18–64, Bonn, Germany No differences Gomes et al., 2012 [26 ] LINE-1 ELISA 126 individuals aged 60–88, Brazil No differences Hou et al., 2010 [27 ] LINE-1 Pyrosequencing 421 individuals aged 21–79 in Warsaw, Poland No differences Data was stratified by gender. Before stratification, association with age was significant Hsiung et al., 2007 [28 ] LINE-1 COBRA PCR 765 individuals aged 18–75, Greater Boston Metropolitan Area No differences Adjusted for sex, race, smoking, alcohol, HPV serology, dietary folate, MTHFR Karami et al., 2015 [29 ] LINE-1 Pyrosequencing PLCO - 436 controls from individuals aged 55–74 in the US, ATBC - 575 controls from individuals aged 55–69 in Finland PLCO: No differences ATBC, increased age associated with higher methylation levels. Age 53-54 has 78.34 LINE-1 methylation%, 55–59 has 78.42 LINE-1 methylation%, 60–64 has 78.68 LINE-1 methylation%, 65–69 has 79.34 LINE-1 methylation%, 70–76 has 79.60 LINE-1 methylation% Liao et al., 2011 [30 ] LINE-1 Pyrosequencing 654 individuals aged 20–79 from the Central and Eastern European Renal Cancer Study (CEERCC) No differences Marques-Rocha et al., 2016 [31 ] LINE-1 MS-HRM 156 individuals aged 19–27, Brazil No differences Mirabello et al., 2010 [32 ] LINE-1 Pyrosequencing 314 individuals aged 12–75+ from the NCI Clinical Genetics Branch Familial TGTC Study in the US No differences Adjusted for sex Pearce et al., 2012 [33 ] LINE-1 Pyrosequencing 228 individuals aged 49–51 from Newcastle, England No differences Perng et al., 2014 [34 ] LINE-1 Pyrosequencing 987 adults aged 45–84 from the Multi-Ethnic Study of Atherosclerosis (MESA), NY & LA No differences Wilhelm et al., 2010 [35 ] LINE-1 Pyrosequencing 465 individuals aged 25–74, from NH No differences Xu et al., 2012 [11 ] LINE-1 Pyrosequencing 1101 women aged 20–98, from The Long Island Breast Cancer Study Project No differences Zhang et al., 2011 [36 ] LINE-1 Pyrosequencing 161 individuals aged 45–75 from the North Texas Healthy Heart Study No differences Zhang et al., 2012 [37 ] LINE-1 Pyrosequencing 165 individuals aged 18–78 from the COMIR (Commuting Mode and Inflammatory Response) study, NY No differences Zhu et al., 2012 [38 ] LINE-1 Pyrosequencing 1465 individuals total from a combination of 5 individual studies across MA; Warsaw, Poland; Milan, Italy; Brescia, Italy; Trissino, Italy No differences Bollati et al., 2009 [22 ] Alu Pyrosequencing 718 individuals aged 55–92 from the Boston Area Normative Aging Study Significant differences ( Increased age associated with an average 0.2 5-mdC percentage decrease Fraga et al., 2005 [39 ] Alu Total 5-mdC content: HPCE 80 monozygotic twins aged 3–74, Spain Significant differences ( Youngest pairs of MZ twins epigenetically similar, whereas oldest pairs clearly distinct Kim et al., 2010 [40 ] Alu Pyrosequencing 86 individuals aged 42–69, South Korea Significant differences ( Statistically significant inverse association with DNA methylation. Adjusted for age Na et al., 2014 [41 ] Alu Pyrosequencing 244 women aged 20–51, Korea No differences Rusiecki et al., 2008 [42 ] Alu Pyrosequencing 70 individuals aged 19–67 from Greenlandic Inuit, Greenland No differences Zhu et al., 2012 [38 ] Alu Pyrosequencing 1465 individuals total from a combination of 5 individual studies across MA; Warsaw, Poland; Milan, Italy; Brescia, Italy; Trissino, Italy No differences Choi et al., 2009 [1 ] 5-mdC LC/ESI-MS/MS 180 women aged 35–75 No differences Fraga et al., 2005 [39 ] 5-mdC Total 5-mdC content: HPCE 80 monozygotic twins aged 3–74, Spain Significant differences ( Youngest pairs of MZ twins epigenetically similar, whereas oldest pairs clearly distinct Fuke et al., 2004 [43 ] 5-mdC HPLC 76 individuals aged 4–94 Significant differences ( Increased age associated with decreased methylation levels. Age 4–14 has 4.018% metC/dC + metC, age 16–22 has 4.03%, age 25–41 has 3.977%, and age 51–94 has 3.948% Moore et al., 2008 [44 ] 5-mdC HPCE, HpaII digest, densitometry 397 individuals aged 20–81 from the Spanish Bladder Cancer Study, Spain No differences Sex Andreotti et al., 2014 [45 ] LINE-1 Pyrosequencing 676 individuals aged 55–74 from the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) in the US Significant differences ( Males had 84.2% average LINE-1 methylation%, Females had 83.5% average LINE-1 methylation% Cash et al., 2012 [46 ] LINE-1 Pyrosequencing 528 individuals aged 25–74 from the Residents Registry of the Shanghai Municipal Government, China Significant differences ( Males had 82.09 average LINE-1 methylation%, Females had 81.53% average LINE-1 methylation% Chalitchagorn et al., 2004 [23 ] LINE-1 COBRA PCR 32 individuals ranging in age, Thailand No differences El-Maarri et al., 2011 [25 ] LINE-1 Pyrosequencing, SIRPH 500 individuals aged 18–64, Bonn, Germany Significant differences ( Average gender difference 0.94% Hou et al., 2010 [27 ] LINE-1 Pyrosequencing 421 individuals aged 21–79 in Warsaw, Poland No differences Hsiung et al., 2007 [28 ] LINE-1 Cobra PCR 765 individuals aged 18–75, Greater Boston Metropolitan Area Significant differences ( Not given; adjusted for age, race, smoking, alcohol, HPV serology, dietary folate, MTHFR Karami et al., 2015 [29 ] LINE-1 Pyrosequencing PLCO, 436 controls from individuals aged 55–74 in the US PLCO, Significant differences ( Males had 77.15% average LINE-1 methylation%, females had 76.58% average LINE-1 methylation% Liao et al., 2011 [30 ] LINE-1 Pyrosequencing 654 individuals aged 20–79 from the Central and Eastern European Renal Cancer Study (CEERCC) Significant differences ( Males had 81.97% average LINE-1 methylation%, females had 81.4% average LINE-1 methylation% Mirabello et al., 2010 [32 ] LINE-1 Pyrosequencing 314 individuals aged 12–75+ from the NCI Clinical Genetics Branch Familial TGTC Study in the US Significant differences ( Males had 79.6% average LINE-1 methylation%, females had 78.87% average LINE-1 methylation%. Adjusted for age Pearce et al., 2012 [33 ] LINE-1 Pyrosequencing 228 individuals aged 49–51 from Newcastle, England No differences Perng et al., 2014 [34 ] LINE-1 Pyrosequencing 987 adults aged 45–84 from the Multi-Ethnic Study of Atherosclerosis (MESA), NY & LA Significant differences ( Males had 80.94% average LINE-1 methylation%, Females had 80.54% average LINE-1 methylation% Rusiecki et al., 2008 [42 ] LINE-1 Pyrosequencing 70 individuals aged 19–67 from Greenlandic Inuit, Greenland Significant differences ( Males had 79.05% average LINE-1 methylation%, Females had 77.73% average LINE-1 methylation% Tajuddin et al., 2013 [47 ] LINE-1 Pyrosequencing 892 individuals aged 20–81 from the Spanish Bladder Cancer/EPICURO study, Spain No differences Significant differences ( Wilhelm et al., 2010 [35 ] LINE-1 Pyrosequencing 465 individuals aged 25–74, from NH Significant differences ( Not given Zhang et al., 2011 [36 ] LINE-1 Pyrosequencing 161 individuals aged 45–75 from the North Texas Healthy Heart Study Significant differences ( Males had 75% average LINE-1 methylation%, females had 73.2% average LINE-1 methylation% Zhang et al., 2012 [37 ] LINE-1 Pyrosequencing 165 individuals aged 18–78 from the COMIR (Commuting Mode and Inflammatory Response) study, NY No differences Zhu et al., 2012 [38 ] LINE-1 Pyrosequencing 1465 individuals total from a combination of 5 individual studies across MA; Warsaw, Poland; Milan, Italy; Brescia, Italy; Trissino, Italy No differences El-Maarri et al., 2007 [48 ] Alu SIRPH 192 individuals aged 18–43, Bonn, Germany Significant differences ( Slightly higher methylation in males Kim et al., 2010 [40 ] Alu Pyrosequencing 86 individuals aged 42–69, South Korea No differences Adjusted for age Rusiecki et al., 2008 [42 ] Alu Pyrosequencing 70 individuals aged 19–67 from Greenlandic Inuit, Greenland Significant differences ( Males had 25.35% average Alu methylation%, Females had 24.69% average Alu methylation% Zhu et al., 2012 [38 ] Alu Pyrosequencing 1465 individuals total from a combination of 5 individual studies across MA; Warsaw, Poland; Milan, Italy; Brescia, Italy; Trissino, Italy No differences Fuke et al., 2004 [43 ] 5-mdC HPLC 76 individuals aged 4–94 Significant differences ( Males had metC/(dC + metC) = 4.01 ± 0.069, females had metC/(dC + metC) = 3.975 ± 0.067 Race/Ethnicity Hsiung et al., 2007 [28 ] LINE-1 Cobra PCR 765 individuals aged 18–75, Greater Boston Metropolitan Area Significant differences ( Not provided; Adjusted for age, sex, smoking, alcohol, HPV serology, dietary folate, MTHFR Perng et al., 2014 [34 ] LINE-1 Pyrosequencing 987 adults aged 45–84 from the Multi-Ethnic Study of Atherosclerosis (MESA), NY & LA Significant differences ( Caucasian Whites had 80.5% average LINE-1 methylation%, African-American Blacks had 80.84% average LINE-1 methylation%, Hispanics had 80.75% average LINE-1 methylation% Xu et al., 2012 [11 ] LINE-1 Pyrosequencing 1101 women aged 20–98, from The Long Island Breast Cancer Study Project No differences Zhang et al., 2011 [36 ] LINE-1 Pyrosequencing 161 individuals aged 45–75 from the North Texas Healthy Heart Study Significant differences ( Non-Hispanic Whites had 75.3% average LINE-1 methylation%, non-Hispanic Blacks had 73.1% average LINE-1 methylation%, Hispanics had 74% average LINE-1 methylation% Zhang et al., 2012 [37 ] LINE-1 Pyrosequencing 165 individuals aged 18–78 from the COMIR (Commuting Mode and Inflammatory Response) study, NY No differences Choi et al., 2009 [1 ] 5-mdC LC/ESI-MS/MS 180 women aged 35–75 No differences Education Agodi et al., 2015 [21 ] LINE-1 Pyrosequencing 177 women aged 13–50, Helsinki No differences Hou et al., 2010 [27 ] LINE-1 Pyrosequencing 421 individuals aged 21–79 in Warsaw, Poland No differences Karami et al., 2015 [29 ] LINE-1 Pyrosequencing PLCO - 436 controls from individuals aged 55–74 in the US, ATBC - 575 controls from individuals aged 55–69 in Finland PLCO -No differences Perng et al., 2014 [34 ] LINE-1 Pyrosequencing 987 adults aged 45–84 from the Multi-Ethnic Study of Atherosclerosis (MESA), NY & LA No differences Zhang et al., 2011 [36 ] LINE-1 Pyrosequencing 161 adults aged 45–75 from the North Texas Healthy Heart Study No differences Choi et al., 2009 [1 ] 5-mdC LC/ESI-MS/MS 180 women aged 35–75 No differences
