rs8192678

A literature review of 70 studies examining single nucleotide polymorphisms (SNPs) associated with obesity in Mexican populations published 2011-2021. The authors identified SNPs with differential behavior in Mexican compared to Caucasian populations, including rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF), rs7498665 (SH2B1), and notably rs6232 (PCSK1) associated with early-onset obesity in Mexican youth. The review emphasizes ethnicity-dependent genetic effects on BMI heritability (40-70%) and highlights genes involved in cholesterol metabolism and adipokine signaling pathways.

This study examined associations between PPARGC1A and PPARGC1B variants and cardiometabolic traits in 3,234 participants of the Diabetes Prevention Program. PPARGC1A variation was strongly associated with baseline triacylglycerol (p=2.9×10⁻³⁰), BMI (p=2.0×10⁻⁵), and changes in these traits at 1 year. The Gly482Ser variant (rs8192678) was associated with subcutaneous adiposity and insulin resistance, while rs2970852 modified metformin's effect on triacylglycerols (p=0.04).

This comprehensive review examines the genetic background of nonalcoholic fatty liver disease (NAFLD), focusing on variants identified by genome-wide association studies (GWAS) and candidate gene studies. The most significant GWAS-identified variants are PNPLA3 rs738409 (I148M), which strongly associates with increased liver steatosis, fibrosis severity, and HCC risk (12-fold increased risk for homozygous carriers), and TM6SF2 rs58542926 (E167K), which increases NASH progression but reduces cardiovascular risk. The review also discusses numerous candidate genes involved in lipid and glucose metabolism and liver injury mechanisms.

A randomized controlled intervention study in 68 obese men tested the effects of polyphenol-rich cloudy apple juice (750 mL/day for 4 weeks) on obesity-related markers and diet-gene interactions. Cloudy apple juice significantly reduced percent body fat (Δ: -1.0 ± 1.3% vs control -0.2 ± 0.9%, p < 0.05) and increased lean body mass. The IL-6-174 G/C polymorphism (rs1800795) showed significant interaction with body fat reduction: only C/C carriers showed significant fat loss with apple juice consumption (p = 0.011 for interaction), while G/C and G/G carriers did not respond.

Comprehensive review of genetic background in nonalcoholic fatty liver disease (NAFLD). The PNPLA3 I148M variant (rs738409 C>G) is identified as a major genetic player strongly associated with increased liver fat content, NASH development, fibrosis severity, and HCC risk. The TM6SF2 E167K variant (rs58542926) emerges as another key contributor to NAFLD pathogenesis and disease progression. Multiple additional GWAS-identified variants and candidate genes are reviewed for their roles in NAFLD susceptibility and progression.

In a study of 1,563 European ancestry participants at increased type 2 diabetes risk, the ENPP1 K121Q polymorphism (rs1044498) did not show cross-sectional association with insulin sensitivity. However, during a 9-month lifestyle intervention in 342 participants, minor allele (Q) carriers showed significantly impaired improvement in insulin sensitivity (p=0.0067 additive, p=0.0027 dominant), suggesting K121Q determines individual susceptibility to the insulin-sensitizing effects of lifestyle intervention.

This case-control study of 1,423 Russian athletes and 1,132 controls examined 15 metabolic gene polymorphisms associated with elite endurance athlete status. Ten 'endurance alleles' were identified: rs4253778 (PPARA), rs2016520 (PPARD), rs8192678 (PPARGC1A), rs7732671 (PPARGC1B), rs1937 (TFAM), rs660339 (UCP2), rs1800849 (UCP3), rs2010963 (VEGFA), NFATC4 rs2229309, and PPP3R1 promoter 5I. The proportion of subjects with ≥9 endurance alleles was significantly higher in elite endurance athletes versus controls (85.7% vs 37.8%, P=7.6×10⁻⁶). The number of endurance alleles positively correlated with slow-twitch muscle fiber proportion (r=0.50, P=4.0×10⁻⁴) and maximal oxygen consumption (r=0.46, P=7.0×10⁻⁴).

This candidate gene association study tested 35 tagging SNPs across PPARGC1A in 2,101 Danish and Estonian children from the European Youth Heart Study, finding nominally significant associations with BMI (rs10018239, p=0.039), waist circumference (rs7656250, rs8192678, rs3755863, rs10018239; p=0.002-0.043), systolic blood pressure (rs2970869, p=0.018), aerobic fitness (rs7656250, rs13117172; p=0.002-0.008), and fasting glucose (rs7657071, rs11724368; p=0.002-0.045). However, none of these associations remained significant after correction for multiple comparisons, suggesting PPARGC1A variation has only modest effects on metabolic and cardiovascular traits in children.

This case-control study of 1,881 Scandinavian women (649 with gestational diabetes mellitus, 1,232 controls) found that the TCF7L2 rs7903146 variant confers increased risk of gestational diabetes mellitus, with heterozygotes showing OR=1.56 (95% CI 1.26-1.93, p=3.7×10⁻⁵) and homozygotes OR=2.05 (95% CI 1.41-2.99, p=0.0001). Four other polymorphisms previously associated with type 2 diabetes (ADIPOQ rs1501299, PPARG rs1801282, PPARGC1A rs8192678, FOXC2 -512C>T, ADRB3 rs4994) were not significantly associated with gestational diabetes mellitus in this population.

In 691 healthy middle-aged Europeans, the PPARGC1A Ser482 allele (Gly482Ser, rs8192678) was associated with elevated non-esterified fatty acid (NEFA) levels at 30 min (p=0.02) and 2 h (p=0.01) and with NEFA AUC (p=0.019) following an oral glucose challenge. The association was significantly stronger in obese individuals (p=0.028 to p=0.005 across time points) than in lean individuals (p>0.6), suggesting obesity modifies the genotype effect on NEFA clearance.

This meta-analysis demonstrates that TCF7L2 rs7903146 T allele is reproducibly associated with type 2 diabetes across multiple ethnic groups. The authors analyzed 29,195 control subjects and 17,202 T2D cases across 29 studies, finding a pooled odds ratio of 1.46 [1.42-1.51] (p=5.4×10−140). The rs7903146 variant showed the strongest and most consistent association with T2D compared to other known diabetes susceptibility genes, with allelic ORs of 1.56 [1.29-1.89] in Moroccans and 1.52 [1.29-1.78] in Austrians.

Erratum correcting the rsID for the PGC1α p.Gly482Ser polymorphism from rs8192673 to rs8192678 in the original study examining interactions between UCP2 -866G/A, mtDNA 10398G/A, and PGC1α polymorphisms in type 2 diabetes susceptibility in a North Indian population.

This journal issue contains multiple genetic association studies on rheumatoid arthritis (RA). A key REMARCA study (146 aCCP+ RA patients vs 314 controls) identified polymorphisms in CTLA4 (rs231775 +49A/G), IL10 (rs1800872 -592A/C), and IL6R (rs8192284 +358A/C) associated with high inflammatory disease activity, with CTLA4 and IL10 minor alleles showing increased risk (OR=1.4, p=0.02 and OR=1.9, p<0.0001 respectively) and IL6R minor allele being protective (OR=0.7, p=0.03). A separate study analyzed NOS3, PPARG, PPARGC1A, PPARGC1B and PAI1 polymorphisms in 73 RA patients for cardiovascular risk.