OBJECTIVES: To investigate the combined effect of FTO rs9930501, rs9930506, and rs9932754 and ADRB2 rs1042713 and rs1042714 using PRS on (1) the odds of obesity and (2) post-intervention differences in dietary, anthropometric, and cardiometabolic parameters in response to high-protein calorie-restricted, high-vitamin E, high-fiber (Hipcref) diet intervention in Malaysian adults.
METHODS: Both a cross-sectional study (n = 178) and a randomized controlled trial (RCT) (n = 128) were conducted to test the aforementioned objectives. PRS was computed as the weighted sum of the risk alleles possessed by each individual participant. Participants were stratified into first (PRS 0-0.64), second (PRS 0.65-3.59), and third (PRS 3.60-8.18) tertiles.
RESULTS: The third tertile of PRS was associated with significantly higher odds of obesity: 2.29 (95% CI = 1.11-4.72, adjusted p = 0.025) compared to the first tertile. Indians (3.9 ± 0.3) had significantly higher PRS compared to Chinese (2.1 ± 0.4) (p = 0.010). In the RCT, a greater reduction in high-sensitivity C-reactive protein (hsCRP) levels was found in second and third tertiles after Hipcref diet intervention compared to the control diet (p interaction = 0.048).
CONCLUSION: Higher PRS was significantly associated with increased odds of obesity. Individuals with higher PRS had a significantly greater reduction in hsCRP levels after Hipcref diet compared to the control diet.
METHODS: A case-control study was conducted involving 600 people with type 2 diabetes (300 chronic kidney disease cases, 300 controls) who participated in The Malaysian Cohort project. Retrospective subanalysis was performed on the chronic kidney disease cases to assess chronic kidney disease progression from the recruitment phase. We genotyped 32 single nucleotide polymorphisms using mass spectrometry. The probability of chronic kidney disease and predicted rate of newly detected chronic kidney disease progression were estimated from the significant gene-environment interaction analyses.
RESULTS: Four single nucleotide polymorphisms (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and five environmental factors (age, sex, smoking, waist circumference and HDL) were significantly associated with chronic kidney disease. Gene-environment interaction analyses revealed significant probabilities of chronic kidney disease for sex (PPARGC1A rs8192678), smoking (eNOS rs2070744, PPARGC1A rs8192678 and KCNQ1 rs2237895), waist circumference (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and HDL (eNOS rs2070744 and PPARGC1A rs8192678). Subanalysis indicated that the rate of newly detected chronic kidney disease progression was 133 cases per 1000 person-years (95% CI: 115, 153), with a mean follow-up period of 4.78 (SD 0.73) years. There was a significant predicted rate of newly detected chronic kidney disease progression in gene-environment interactions between KCNQ1 rs2283228 and two environmental factors (sex and BMI).
CONCLUSIONS: Our findings suggest that the gene-environment interactions of eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228 with specific environmental factors could modify the probability for chronic kidney disease.
SETTING: 545 communities from 17 high-income, upper-middle, low-middle and low-income countries (HIC, UMIC, LMIC, LIC) involved in the Environmental Profile of a Community's Health (EPOCH) study from 2009 to 2014.
PARTICIPANTS: Community audits and surveys of adults (35-70 years, n=12 953).
PRIMARY AND SECONDARY OUTCOME MEASURES: Summary scores of tobacco policy implementation (cost and availability of cigarettes, tobacco advertising, antismoking signage), social unacceptability and knowledge were associated with quit ratios (former vs ever smokers) using multilevel logistic regression models.
RESULTS: Average tobacco control policy score was greater in communities from HIC. Overall 56.1% (306/545) of communities had >2 outlets selling cigarettes and in 28.6% (154/539) there was access to cheap cigarettes (<5cents/cigarette) (3.2% (3/93) in HIC, 0% UMIC, 52.6% (90/171) LMIC and 40.4% (61/151) in LIC). Effective bans (no tobacco advertisements) were in 63.0% (341/541) of communities (81.7% HIC, 52.8% UMIC, 65.1% LMIC and 57.6% LIC). In 70.4% (379/538) of communities, >80% of participants disapproved youth smoking (95.7% HIC, 57.6% UMIC, 76.3% LMIC and 58.9% LIC). The average knowledge score was >80% in 48.4% of communities (94.6% HIC, 53.6% UMIC, 31.8% LMIC and 35.1% LIC). Summary scores of policy implementation, social unacceptability and knowledge were positively and significantly associated with quit ratio and the associations varied by gender, for example, communities in the highest quintile of the combined scores had 5.0 times the quit ratio in men (Odds ratio (OR) 5·0, 95% CI 3.4 to 7.4) and 4.1 times the quit ratio in women (OR 4.1, 95% CI 2.4 to 7.1).
CONCLUSIONS: This study suggests that more focus is needed on ensuring the tobacco control policy is actually implemented, particularly in LMICs. The gender-related differences in associations of policy, social unacceptability and knowledge suggest that different strategies to promoting quitting may need to be implemented in men compared to women.