Trends of LSS rs2254524, LSS rs2254522, and NEDD4L rs4149601 Genetic Variants of Hypertension Among Obese Adolescents

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Obesity and hypertension in adolescents (n=202). Intervention: LSS (rs2254524, rs2254522) and NEDD4L (rs4149601) genetic variants and urinary Na/K ratio vs. Wild-type genotypes (LSS rs2254524 AA, LSS rs2254522 AA, NEDD4L rs4149601 GG) and normotensive group. Primary outcome: Hypertension status (systolic and/or diastolic blood pressure >130/80 mmHg) associated with LSS rs2254524 variant (AC/CC vs wild-type AA) (OR 0.783, 95% CI 0.29-2.07, p=0.6210).

Q: What does this research mean for the field?

Genetic variants in LSS (rs2254524, rs2254522) and NEDD4L (rs4149601) as well as urinary sodium-to-potassium ratios are not significantly associated with hypertension in obese adolescents, whereas adiposity and male sex are the predominant correlates. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Fitrisia Amelin; Rinang Mariko; Nur Indrawaty Lipoeto; Arni Amir

doi:10.18585/inabj.v18i5.4322

November 14, 2026The Indonesian Biomedical JournalOpen Access

Trends of LSS rs2254524, LSS rs2254522, and NEDD4L rs4149601 Genetic Variants of Hypertension Among Obese Adolescents

View Full Paper

Ask AI

Bookmark

Share

Key result

LSS (rs2254524, rs2254522) and NEDD4L (rs4149601) genetic variants and urinary Na/K ratio were not associated with hypertension in obese adolescents.

Why the study?

Polymorphisms in renal sodium handling genes such as LSS and NEDD4L and the urinary sodium-to-potassium ratio have been proposed as blood pressure determinants in obese adolescents, but evidence on gene-environment interactions remains limited.

Are genetic polymorphisms in LSS (rs2254524, rs2254522) and NEDD4L (rs4149601) or the spot urinary sodium-to-potassium ratio associated with hypertension in obese adolescents?

Key Points

To examine associations between LSS (rs2254524, rs2254522) and NEDD4L (rs4149601) genetic polymorphisms, urinary sodium-to-potassium ratio, and hypertension among obese adolescents.
Cross-sectional comparative study conducted among 202 obese adolescents aged 15–18 years (101 hypertensive, 101 normotensive) in Padang, Indonesia.
Genotypes were identified via PCR and Sanger sequencing, and spot urinary sodium and potassium were quantified using an ion-selective electrode method.
Male gender (64.9% vs. 35.1%), body weight, height, BMI percentile, and waist circumference were significantly higher in hypertensive participants (all p<0.0001).
No significant associations were observed between hypertension and genotypes for LSS rs2254524 (p=0.2110), LSS rs2254522 (p=0.2150), or NEDD4L rs4149601 (p>0.05).
Urinary sodium-to-potassium ratio showed no significant difference between hypertensive and normotensive groups (p=0.889).

Study Design

Type

Cross-Sectional (n=202)

Multicenter

Yes

Structured PICO

Are genetic polymorphisms in LSS (rs2254524, rs2254522) and NEDD4L (rs4149601) or the spot urinary sodium-to-potassium ratio associated with hypertension in obese adolescents?

P

Population

202 obese Indonesian adolescents aged 15-18 years (101 hypertensive and 101 normotensive, 45.0% female), free of kidney disease or antihypertensive medication use, evaluated in a cross-sectional study.

E

Exposure

Genetic variants in lanosterol synthase (LSS rs2254524 A>C, LSS rs2254522 A>G) and neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L rs4149601 G>A) determined by PCR and Sanger sequencing, and spot urinary sodium-to-potassium (Na/K) ratio measured via ion-selective electrode from second morning fasting void

C

Comparator

Wild-type genotypes (AA for LSS rs2254524, AA for LSS rs2254522, GG for NEDD4L rs4149601) and normotensive obese adolescents (n=101)

O

Outcome

Prevalence of hypertension (defined as elevated systolic and/or diastolic blood pressure >130/80 mmHg per 2017 American Academy of Pediatrics Clinical Practice Guideline) and its association with LSS and NEDD4L genotypes and urinary Na/K ratiosurrogate

Main Result

Odds Ratio: 0.783 (95% CI 0.29–2.07)

Absolute Event Rate: 50.5% vs 44.4%

p-value: p=0.6210

In obese Indonesian adolescents, male sex and greater adiposity (BMI percentile and waist circumference) are the dominant correlates of hypertension, overshadowing any statistically significant effects from LSS and NEDD4L renal sodium-handling gene variants or spot urinary Na/K ratio.

Limitations

Cross-sectional design and equal group sizes preclude causal inference and reduce precision of prevalence estimates
Small sample size limiting statistical power
Unassessed pubertal status
Reliance on spot urinary Na/K ratio rather than 24-hour urine collection, which is subject to misclassification
Lack of formal control for population stratification and no multiplicity corrections applied
Small sample size with limited statistical power compared to larger cohorts
Reliance on spot urinary Na/K ratio rather than 24-hour urine collection, introducing measurement inaccuracy and potential misclassification bias toward the null
Lack of formal control for population stratification
No multiplicity corrections applied

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Adiposity and male sex predominate as hypertension correlates in obese adolescents; leaves open LSS/NEDD4L variant roles in other cohorts.

Abstract

BACKGROUND: Polymorphisms in genes regulating renal sodium handling, such as lanosterol synthase (LSS) and neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L), as well as the urinary sodium-to-potassium (Na/K) ratio have been proposed as determinants of blood pressure among obese adolescents, but evidence on gene-environment interactions remains limited. This study was conducted to examine associations between LSS (rs2254524) and NEDD4L (rs4149601) polymorphisms and the urinary Na/K ratio and hypertension in obese adolescents.METHODS: This cross-sectional comparative study enrolled 202 obese adolescents (101 hypertensive, 101 normotensive) aged 15–18 years old. Genotyping was performed by polymerase chain reaction (PCR) followed by Sanger sequencing. An ion-selective electrode was used to measure the spot urinary sodium and potassium for the calculation of Na/K ratio. Associations of the gene polymorphism and urinary sodium and potassium interaction were then statistically analyzed.RESULTS: Male gender, body weight, height, body mass index (BMI), and waist circumference were significantly higher in the hypertensive group (all p<0.0001). Though hypertension was numerically more common among obese adolescents carrying LSS variants (rs2254524, rs2254522) and NEDD4L variant (rs4149601), neither LSS (A>C, A>G) nor NEDD4L genotypes were significantly associated with hypertension in bivariate analyses (all p>0.05). The urinary Na/K ratio did not differ between groups (p=0.889).CONCLUSION: Genetic variants of LSS rs2254524, LSS rs2254522, and NEDD4L rs4149601 are showing trends of hypertension among obese adolescents in this study. Greater adiposity and male gender, by contrast, were significantly associated with hypertension and remained the dominant correlates of blood pressure.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Amelin et al. (2026) conducted a cross-sectional in Obesity and hypertension in adolescents (n=202). LSS (rs2254524, rs2254522) and NEDD4L (rs4149601) genetic variants and urinary Na/K ratio vs. Wild-type genotypes (LSS rs2254524 AA, LSS rs2254522 AA, NEDD4L rs4149601 GG) and normotensive group was evaluated on Hypertension status (systolic and/or diastolic blood pressure >130/80 mmHg) associated with LSS rs2254524 variant (AC/CC vs wild-type AA) (OR 0.783, 95% CI 0.29-2.07, p=0.6210). LSS (rs2254524, rs2254522) and NEDD4L (rs4149601) genetic variants and urinary Na/K ratio were not associated with hypertension in obese adolescents.

synapsesocial.com/papers/6af9ebcdd393cbc380a05014 https://doi.org/10.18585/inabj.v18i5.4322

View Full Paper

Ask AI

Bookmark

Share

Trends of LSS rs2254524, LSS rs2254522, and NEDD4L rs4149601 Genetic Variants of Hypertension Among Obese Adolescents

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Trends of LSS rs2254524, LSS rs2254522, and NEDD4L rs4149601 Genetic Variants of Hypertension Among Obese Adolescents

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading