Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, Mexico.
Gene. 2013 May 15;520(2):185-8. doi: 10.1016/j.gene.2013.03.038. Epub 2013 Mar 17.
Non-alcoholic fatty liver disease (NAFLD) and elevated alanine transaminase (ALT) levels are common in obese Hispanic adults and children. Recently, a PNPLA3 gene variant (I148M) was strongly associated with NAFLD and higher ALT levels in obese adults, including Hispanics. The aims of this study were to estimate the frequency of elevated ALT levels, and to address the influence of obesity and PNPLA3/I148M on ALT levels in a general population sample of Mexican school-aged children.
A total of 1037 non-related Mexican children aged 6 to 12 years were genotyped for the I148M variant. Anthropometric, clinical and metabolic parameters were collected from all participants.
Elevated ALT levels (>35 U/L) were more frequent in obese (26.9%) and overweight (9.3%) than in normal weight children (2.2%). The M148M genotype was significantly associated with elevated ALT levels in this population (OR=3.7, 95% CI 2.3-5.9; P=3.7×10(-8)), and children carrying the M148M genotype showed significantly lower HDL cholesterol levels and BMI z-core (P=0.036 and 0.015, respectively). On stratifying by BMI percentile, this genotype conferred a much greater risk of elevated ALT levels in normal weight (OR=19.9, 95% CI 2.5-157.7; P=0.005) than overweight and obese children (OR=3.4, 95% CI 1.3-8.9; P=0.014 and OR=3.1, 95% CI 1.7-5.5; P=1.4 x10(-4), respectively).
The I148M PNPLA3 variant is strongly associated with elevated ALT levels in normal weight and overweight/obese Mexican children. Thus, the M148M genotype may be considered as an important risk factor for liver damage in this population.
非酒精性脂肪性肝病（NAFLD）和丙氨酸转氨酶（ALT）水平升高在肥胖的西班牙裔成年人和儿童中很常见。最近，一种 PNPLA3 基因变异（I148M）与肥胖成年人中的 NAFLD 和更高的 ALT 水平密切相关，包括西班牙裔。本研究的目的是评估 ALT 水平升高的频率，并研究肥胖和 PNPLA3/I148M 对墨西哥学龄儿童一般人群 ALT 水平的影响。
共对 1037 名无亲缘关系的 6 至 12 岁的墨西哥儿童进行了 I148M 变异体的基因分型。所有参与者均采集了人体测量、临床和代谢参数。
ALT 水平升高（>35 U/L）在肥胖（26.9%）和超重（9.3%）儿童中比体重正常儿童（2.2%）更为常见。在该人群中，M148M 基因型与 ALT 水平升高显著相关（OR=3.7，95%CI 2.3-5.9；P=3.7×10(-8)），携带 M148M 基因型的儿童 HDL 胆固醇水平和 BMI z 分数明显降低（P=0.036 和 0.015）。按 BMI 百分位分层，该基因型在体重正常儿童中导致 ALT 水平升高的风险显著增加（OR=19.9，95%CI 2.5-157.7；P=0.005），而在超重和肥胖儿童中则不明显（OR=3.4，95%CI 1.3-8.9；P=0.014 和 OR=3.1，95%CI 1.7-5.5；P=1.4 x10(-4)）。
PNPLA3 基因 I148M 变异与正常体重和超重/肥胖墨西哥儿童 ALT 水平升高密切相关。因此，M148M 基因型可被视为该人群肝损伤的一个重要危险因素。
