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Liver damage severity in obese children affected by ethnicity, genetic polymorphisms

Obese African-American children had less severe liver damage than Caucasians and Hispanics, and genetic polymorphisms were found to influence injury severity in a recent study.

Researchers evaluated 229 obese children (mean age, 12.8 years; mean BMI, 31.4 ± 7.4), including 87 Caucasians, 61 African-Americans and 81 Hispanics. All patients received MRI, underwent oral glucose tolerance testing and were assessed for levels of nonalcoholic steatohepatitis (NASH) biomarker cytokeratin-18 (CK-18). Genotyping also was performed to determine any impact gene variants rs738409 in the PNPLA3 and rs2645424 in the FDFT1 had on damage severity.

Patients with NASH (n=12) had higher hepatic fat content (HFF; P=.008) and CK-18 levels (P<.0001) and lower whole body insulin sensitivity index (WBISI) (P=.02) than the remaining cohort. African-American patients had significantly lower CK-18 levels compared with Caucasian (P=.004) and Hispanic children (P<.001).

Investigators observed associations between CK-18 levels and HFF and WBISI among Caucasian (P=.0018 for HFF; P<.0001 for WBISI) and Hispanic patients (P<.0001 for HFF; P=.02 for WBISI), but not among African-American participants (P=.5 for both). HFF (P=.011) and WBISI (P=.018) were independently associated with ethnicity after adjusting for age, sex and total body fat.

Single nucleotide polymorphisms (SNPs) at rs738409 in the PNPLA3 were independently associated with CK-18 among Caucasians (P=.02) and Hispanics (P=.05). SNPs at rs2645424 in the FDFT1 were similarly associated with CK-18 among Caucasian (P=.05) and Hispanics (P=.02), with a trend toward significance observed among African-Americans (P=.07).

“This study provides the evidence that African-American obese children and adolescents show a lower degree of liver damage than Caucasians and Hispanics, independent of the degree of hepatic fat accumulation and insulin resistance,” the researchers concluded. “These data suggest that African-Americans are protected from hepatic damage even in [the] presence of a high degree of hepatic fat accumulation and insulin resistance. Our observation of a different interethnic propensity to development of liver injury is clinically relevant. This suggests that Hispanic and Caucasian obese children and adolescents require closer follow-up of their liver metabolic status.”